5-Substituted 2-benzylidene-1-tetralone analogues as A 1 and/or A 2A antagonists for the potential treatment of neurological conditions

作者： H.D. Janse van Rensburg , G. Terre'Blanche , M.M. van der Walt , L.J. Legoabe

DOI: 10.1016/J.BIOORG.2017.08.013

关键词:

摘要: Adenosine A1 and A2A receptors are attracting great interest as drug targets for their role in cognitive motor deficits, respectively. Antagonism of both these adenosine may offer therapeutic benefits complex neurological diseases, such Alzheimer's Parkinson's disease. The aim this study was to explore the affinity selectivity 2-benzylidene-1-tetralone derivatives receptor antagonists. Several 5-hydroxy substituted analogues with substituents on ring B were synthesized assessed antagonists via radioligand binding assays. results indicated that hydroxy substitution meta para position phenyl B, displayed highest Ki values low micromolar range. Replacement a 2-amino-pyrimidine moiety led compound 12 an increase receptor. These patterns enhanced affinity. para-substituted analogue 3 behaved GTP shift assay performed rat whole brain membranes expressing receptors. In conclusion, compounds 12, showed best respectively, therefore represent novel have potential further structural modifications candidates disorders.

参考文章(44)

Mietha M. Van der Walt, Gisella Terre’Blanche, 1,3,7-Triethyl-substituted xanthines--possess nanomolar affinity for the adenosine A1 receptor. Bioorganic & Medicinal Chemistry. ,vol. 23, pp. 6641- 6649 ,(2015) , 10.1016/J.BMC.2015.09.012

Maria Grazia Spillantini, Marie Luise Schmidt, Virginia M.-Y. Lee, John Q. Trojanowski, Ross Jakes, Michel Goedert, α-Synuclein in Lewy bodies Nature. ,vol. 388, pp. 839- 840 ,(1997) , 10.1038/42166

Lawrence S. Honig, Relationship between caffeine intake and Parkinson disease. JAMA. ,vol. 284, pp. 1378- 1379 ,(2000) , 10.1001/JAMA.284.11.1378

Kenneth A. Jacobson, Stefano Moro, John A. Manthey, Patrick L. West, Xiao-duo Ji, Interactions of flavones and other phytochemicals with adenosine receptors. Advances in Experimental Medicine and Biology. ,vol. 505, pp. 163- 171 ,(2002) , 10.1007/978-1-4757-5235-9_15

T Murayama, M Ui, [3H]GDP release from rat and hamster adipocyte membranes independently linked to receptors involved in activation or inhibition of adenylate cyclase. Differential susceptibility to two bacterial toxins. Journal of Biological Chemistry. ,vol. 259, pp. 761- 769 ,(1984) , 10.1016/S0021-9258(17)43523-X

E. R. Dorsey, R. Constantinescu, J. P. Thompson, K. M. Biglan, R. G. Holloway, K. Kieburtz, F. J. Marshall, B. M. Ravina, G. Schifitto, A. Siderowf, C. M. Tanner, Projected number of people with parkinson disease in the most populous nations, 2005 through 2030 Neurology. ,vol. 68, pp. 384- 386 ,(2007) , 10.1212/01.WNL.0000247740.47667.03

Bertil B. Fredholm, Jiang-Fan Chen, Rodrigo A. Cunha, Per Svenningsson, Jean-Marie Vaugeois, Adenosine and Brain Function International Review of Neurobiology. ,vol. 63, pp. 191- 270 ,(2005) , 10.1016/S0074-7742(05)63007-3

Koji Yamada, Minoru Kobayashi, Akihisa Mori, Peter Jenner, Tomoyuki Kanda, Antidepressant-like activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents Pharmacology, Biochemistry and Behavior. pp. 23- 30 ,(2013) , 10.1016/J.PBB.2013.10.022

Michael A. Schwarzschild, Luigi Agnati, Kjell Fuxe, Jiang-Fan Chen, Micaela Morelli, Targeting adenosine A2A receptors in Parkinson's disease. Trends in Neurosciences. ,vol. 29, pp. 647- 654 ,(2006) , 10.1016/J.TINS.2006.09.004

10.

S. Ferré, K. Fuxe, G. von Euler, B. Johansson, B.B. Fredholm, Adenosine-dopamine interactions in the brain Neuroscience. ,vol. 51, pp. 501- 512 ,(1992) , 10.1016/0306-4522(92)90291-9

5-Substituted 2-benzylidene-1-tetralone analogues as A 1 and/or A 2A antagonists for the potential treatment of neurological conditions

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5-Substituted 2-benzylidene-1-tetralone analogues as A 1 and/or A 2A antagonists for the potential treatment of neurological conditions

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