Abstract
Using an N-oleoyl ethanolamide scaffold, a series of phosphate polar head group analogues of LPA comprised of various alpha-substituted phosphonates and thiophosphates was prepared. In a broken cell GTP[gamma35S] binding assay, agonist activity was evaluated at the three LPA receptors of the endothelial differentiation gene (Edg) family. This study has resulted in the discovery of a nonhydrolyzable LPA1-selective agonist (11). Additionally, thiophosphate 19 bears an isosteric phosphate mimetic that confers agonism at the LPA1 receptor but not LPA2.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amides / chemistry
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Animals
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Cells, Cultured
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Lysophospholipids / chemical synthesis*
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Lysophospholipids / pharmacology
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Oleic Acids / chemistry
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Phosphates / chemistry*
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Phosphoric Acids / chemistry*
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Radioligand Assay / methods
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Receptors, Lysophosphatidic Acid / agonists*
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Receptors, Lysophosphatidic Acid / metabolism
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Stearic Acids / chemistry
Substances
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Amides
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Lysophospholipids
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Oleic Acids
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Phosphates
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Phosphoric Acids
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Receptors, Lysophosphatidic Acid
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Stearic Acids
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phosphoric acid
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thiophosphoric acid
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isostearic acid