α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors

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Abstract

Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two β-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated α- and β-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of β-hydroxy phosphonates was also studied.

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Cui, P., McCalmont, W. F., Tomsig, J. L., Lynch, K. R., & Macdonald, T. L. (2008). α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors. Bioorganic and Medicinal Chemistry, 16(5), 2212–2225. https://doi.org/10.1016/j.bmc.2007.11.078

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