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ID: ALA1136274

Journal: Bioorg Med Chem Lett

Title: Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: discovery of potent S1P receptor agonists.

Authors: Clemens JJ, Davis MD, Lynch KR, Macdonald TL.

Abstract: Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC(50)=8.6 nM at the S1P(1) receptor using a [gamma-35S]GTP binding assay as compared to an EC(50)=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5).

CiteXplore: 14505636

DOI: 10.1016/s0960-894x(03)00812-6