Journal article

Effects of Conformational Restriction of 2-Amino-3-benzoylthiophenes on A(1) Adenosine Receptor Modulation

Luigi Aurelio, Celine Valant, Bernard L Flynn, Patrick M Sexton, Jonathan M White, Arthur Christopoulos, Peter J Scammells

Journal of Medicinal Chemistry | AMER CHEMICAL SOC | Published : 2010


2-Amino-3-benzoylthiophenes (2A3BTs) have been widely reported to act as allosteric enhancers (AEs) at the A(1) adenosine receptor (A(1)AR). Herein we describe the synthesis of a series of 1-aminoindeno[1,2-c]thiophen-8-ones and a series of (2-aminoindeno[2,1-b]thiophen-3-yl)(phenyl)methanones as conformationally rigid analogues of the 2A3BTs. These compounds were screened using a functional assay of A(1)AR-mediated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in intact Chinese hamster ovary (CHO) cells to identify both potential agonistic effects as well as the ability to allosterically modulate the activity of the orthosteric agonist, N(6)-(R-phenylisopropyl)a..

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University of Melbourne Researchers


Awarded by Australian Research Council

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Funding Acknowledgements

This research was supported by Discovery grant DP0877497 of the Australian Research Council and Program grant 519461 of the National Health and Medical Research Council (NHMRC) of Australia. A.C. is a Senior, and P.M.S. a Principal Research Fellow, of the NHMRC. We are grateful to Dr. Michael Crouch, TGR Biosciences, Adelaide, for generously providing the ERK SureFire Alphascreen kit reagents.