Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: Discovery of quinoxaline-based hybrid compounds with AChE, H 3R and BACE 1 inhibitory activities

Bioorganic and Medicinal Chemistry

Volumn 19, Issue 23, 2011, Pages 7158-7167

  Huang, Wenhai ^a,b   Tang, Li ^a   Shi, Ying ^c   Huang, Shufang ^a   Xu, Lei ^d   Sheng, Rong ^a   Wu, Peng ^a   Li, Jia ^d   Zhou, Naiming ^c   Hu, Yongzhou ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b INSTITUTE OF MATERIA MEDICA   (China)

^c ZHEJIANG UNIVERSITY   (China)

^d National Center for Drug Screening   (China)

Author keywords

AChE; Alzheimer's disease; BACE 1; H 3R; Multi Target Directed Ligands

Indexed keywords

2 (3 AMINOQUINOXALIN 2 YLAMINO) N (1 BENZYLPIPERIDIN 4 YL)ACETAMIDE; 2 (3 AMINOQUINOXALIN 2 YLAMINO) N [4 (PIPERIDIN 1 YLMETHYL)PHENYL]ACETAMIDE; 2 (3 AMINOQUINOXALIN 2 YLAMINO) N [4 (PYRROLIDIN 1 YLMETHYL)PHENYL]ACETAMIDE; 2 AMINE 3 [[4 (PIPERIDIN 1 YLMETHYL)PHENYLAMINO]METHYL]QUINOXALIN; 2 CARBOXAMIDE 3 AMINO N (1 BENZYLPIPERIDIN 4 YL)QUINOXALINE; 2 CARBOXAMIDE 3 AMINO N [4 (PIPERIDIN 1 YLMETHYL)PHENYL]QUINOXALINE; 2,3 DIAMINE N2 [2 [4 (PIPERIDIN 1 YLMETHYL)PHENOXY]ETHYL]QUINAXOLINE; 2,3 DIAMINE N2 [2 [4 [(4 METHYLPIPERAZIN 1 YL)METHYL]PHENOXY]ETHYL]QUINAXOLINE; 2,3 DIAMINE N2 [2 [4 [(DIETHYLAMINO)METHYL]PHENOXY]ETHYL]QUINAXOLINE; 2,3 DIAMINE N2 [3 [4 (PIPERIDIN 1 YLMETHYL)PHENOXY]PROPYL]QUINAXOLINE; 2,3 DIAMINE N2 [4 (PIPERIDIN 1 YLMETHYL)BENZYLIDINE]QUINAXOLINE; 2,3 DIAMINE N2 [4 (PIPERIDIN 1 YLMETHYL)PHENYL]QUINOXALINE; 4 CARBOXAMIDE N (3 AMINOQUINOXALIN 2 YL) 1 BENZYLPIPERIDINE; ACETYLCHOLINESTERASE; BETA SECRETASE 1; BETA SECRETASE INHIBITOR; CHOLINESTERASE INHIBITOR; CYCLIC AMP; DONEPEZIL; HISTAMINE H1 RECEPTOR; HISTAMINE H2 RECEPTOR; HISTAMINE H3 RECEPTOR; HISTAMINE H3 RECEPTOR ANTAGONIST; HISTAMINE H4 RECEPTOR; MULTI TARGET DIRECTED LIGAND; N (3 AMINOQUINOXALIN 2 YL) 4 (PIPERIDIN 1 YLMETHYL)BENZAMIDE; N (3 AMINOQUINOXALIN 2 YL) 4 (PYRROLIDIN 1 YLMETHYL)BENZAMIDE; QUINOXALINE DERIVATIVE; THIOPERAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; ANIMAL TISSUE; ARTICLE; BRAIN HOMOGENATE; CELL STRAIN HEK293; CONTROLLED STUDY; DATA BASE; DRUG ACTIVITY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; MOLECULAR DOCKING; NONHUMAN; PROTEIN BINDING; RAT; SCORING SYSTEM; STRUCTURE ACTIVITY RELATION;

ACETYLCHOLINESTERASE; ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ACID ENDOPEPTIDASES; CHOLINESTERASE INHIBITORS; HISTAMINE H3 ANTAGONISTS; HUMANS; KINETICS; LIGANDS; MODELS, MOLECULAR; QUINOXALINES; RECEPTORS, HISTAMINE H3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 80655136970     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.09.061     Document Type: Article

References (20)

1. K.G. Aurn, K. Nagaswamy, and T. Jordan Curr. Top. Med. Chem. 5 2005 1609
2. G. Tao, and W.H. Doug Curr. Med. Chem. 13 2006 1811
3. R. Morphy, and Z. Rankovic Curr. Pharm. Design. 15 2009 587
4. M.L. Bolognesi, A. Cavalli, L. Valgimigli, M. Bartolini, M. Rosini, V. Andrisano, M. Recanatini, and C. Melchiorre J. Med. Chem. 50 2007 6446
5. Y.P. Zhu, K. Xiao, L.P. Ma, B. Xiong, Y. Fu, H.P. Yu, W.D. Wang, Y. Hu, H.L. Peng, J.Y. Li, Q. Gong, Q. Chai, X.C. Tang, H.Y. Zhang, J. Li, and J.K. Shen Bioorg. Med. Chem. 17 2009 1600
6. J. Marco-Contelles, R. León, C. de los Ríos, A. Samadi, M. Bartolini, V. Andrisano, O. Huertas, X. Barril, F.J. Luque, M.I. Rodríguez-Franco, B. López, M.G. López, A.G. García, M.do C. Carreiras, and M. Villarroya J. Med. Chem. 9 2009 2724
7. P. Blandina, M. Giorgetti, L. Bartolini, M. Cecchi, H. Timmerman, R. Leurs, G. Pepeu, and M.G. Giovannini Br. J. Pharmacol. 119 1996 1656
8. S.D. Bembenek, J.M. Keith, M.A. Letavic, R. Apodaca, A.J. Barbier, L. Dvorak, L. Aluisio, K.L. Miller, T.W. Lovenberg, and I. Nicholas Bioorg. Med. Chem. 16 2008 2968 2973
9. A.Y. Kornilova, and M.S. Wolfe Annu. Rep. Med. Chem. 38 2003 41
10. V. John, J.P. Beck, M.J. Bienkowski, S. Sinha, and R.L. Heinrikson J. Med. Chem. 46 2003 4625
11. P. Magdolna, and K. János Neurochem. Int. 53 2008 103
12. W.H. Huang, H.P. Yu, R. Sheng, J. Li, and Y.Z. Hu Bioorg. Med. Chem. 16 2008 10190
13. R. Sheng, X. Lin, J. Li, Y.K. Jiang, Z.C. Shang, and Y.Z. Hu Bioorg. Med. Chem. Lett. 15 2005 3834
14. R. Leurs, R.A. Bakker, H. Timmerman, and I.J.P. de Esch Nature Rev. Drug Disc. 4 2005 107 120
15. R. Sheng, Y. Xu, C.Q. Hu, J. Zhang, X. Lin, J.Y. Li, B. Yang, Q.J. He, and Y.Z. Hu Eur. J. Med. Chem. 44 2009 7
16. Z. Chen, A.M. Venkatesan, C.M. Dehnhardt, D. Osvaldo, D. Efren, A.K. Semiramis, L. Chen, Y. Geng, K.T. Arndt, J. Lucas, I. Chaudhary, and T.S. Mansour Bioorg. Med. Chem. Lett. 19 2009 4980
17. R. Wang, and Y. Guan Gaodeng Xuexiao Huaxue Xuebao 11 1990 894
18. A.H. Gowenlock, G.T. Newbold, and F.S. Spring J. Chem. Soc. 67 1945 622
19. R.W. Begland, and D.R. Hartter J. Org. Chem. 37 1972 4136
20. E. Schipper, and A.R. Day J. Am. Chem. Soc. 73 1951 5672