Evaluation of short-tether Bis-THA AChE inhibitors. A further test of the dual binding site hypothesis
作者： Paul R. Carlier , Yi Fan Han , Ella S.-H. Chow , Crystal P.-L. Li , Hong Wang
DOI: 10.1016/S0968-0896(98)00213-2
关键词:
摘要: Abstract To provide a further test of the dual binding site hypothesis proposed for acetylcholinesterase (AChE) inhibitor heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) A7A , short-tether (ethylene–hexylene) homologs A2A – A6A were prepared. En route to these compounds, convenient and scaleable syntheses useful pharmaceutical intermediate 9-chloro-1,2,3,4-tetrahydroacridine 3 developed. AChE butyrylcholinesterase (BChE) inhibition assays A10A confirm that seven methylene tether ( ) optimizes potency AChE/BChE selectivity. Finally, studies indicate simultaneous alkylene-linked 9-amino-1,2,3,4-tetrahydroacridine dimers catalytic peripheral sites is possible with length as short 5 methylenes. ©
elsevier.com
sci-hub.se 参考文章(11)
George L. Ellman, K.Diane Courtney, Valentino Andres, Robert M. Featherstone, A new and rapid colorimetric determination of acetylcholinesterase activity Biochemical Pharmacology. ,vol. 7, pp. 88- 95 ,(1961) , 10.1016/0006-2952(61)90145-9
Dimitrios Galanakis, Carole A. Davis, Benedicto Del Rey Herrero, C. Robin Ganellin, Philip M. Dunn, Donald H. Jenkinson, Synthesis and structure : activity relationships of dequalinium analogues as K+ channel blockers : investigations on the role of the charged heterocycle Journal of Medicinal Chemistry. ,vol. 38, pp. 595- 606 ,(1995) , 10.1021/JM00004A005
Yuan-Ping Pang, Polly Quiram, Tanya Jelacic, Feng Hong, Stephen Brimijoin, Highly Potent, Selective, and Low Cost Bis-tetrahydroaminacrine Inhibitors of Acetylcholinesterase STEPS TOWARD NOVEL DRUGS FOR TREATING ALZHEIMER'S DISEASE Journal of Biological Chemistry. ,vol. 271, pp. 23646- 23649 ,(1996) , 10.1074/JBC.271.39.23646
GM Badger, RW Hinde, WE Matthews, TM Spotswood, The Condensation of Cyclohexanone and Anthranilic Acid Australian Journal of Chemistry. ,vol. 16, pp. 732- 733 ,(1963) , 10.1071/CH9630732
Dimitrios Galanakis, Carole A. Davis, C. Robin Ganellin, Philip M. Dunn, Synthesis and Quantitative Structure−Activity Relationship of a Novel Series of Small Conductance Ca2+-Activated K+ Channel Blockers Related to Dequalinium Journal of Medicinal Chemistry. ,vol. 39, pp. 359- 370 ,(1996) , 10.1021/JM950520I
Yuan-Ping Pang, Alan P. Kozikowski, Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies Journal of Computer-aided Molecular Design. ,vol. 8, pp. 669- 681 ,(1994) , 10.1007/BF00124014
Jacob Szmuszkovicz, Eric T. Michalson, Stan D'Andrea, Jeremiah P. Freeman, The synthesis of 9-(1-azetidinyl)-1,2,3,4-tetrahydroacridine Heterocycles. ,vol. 30, pp. 415- 425 ,(1990) , 10.3987/COM-89-S9
M. Harel, J. L. Sussman, E. Krejci, S. Bon, P. Chanal, J. Massoulie, I. Silman, Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 89, pp. 10827- 10831 ,(1992) , 10.1073/PNAS.89.22.10827
X.-M. Cheng, C. Lee, S. Klutchko, T. Winters, E.E. Reynolds, K.M. Welch, M.A. Flynn, A.M. Doherty, Synthesis and structure-activity relationships of 9-substituted acridines as endothelin-A receptor antagonists Bioorganic & Medicinal Chemistry Letters. ,vol. 6, pp. 2999- 3002 ,(1996) , 10.1016/S0960-894X(96)00551-3
Yuan-Ping Pang, Feng Hong, Polly Quiram, Tanya Jelacic, Stephen Brimijoin, Synthesis of alkylene linked bis-THA and alkylene linked benzyl-THA as highly potent and selective inhibitors and molecular probes of acetylcholinesterase Journal of The Chemical Society-perkin Transactions 1. pp. 171- 176 ,(1997) , 10.1039/A601642A