LPA的α-和β-取代膦酸酯类似物作为自分泌运动因子抑制剂。
alpha- and beta-substituted phosphonate analogs of LPA as autotaxin inhibitors.
作者信息
Cui Peng, McCalmont William F, Tomsig Jose L, Lynch Kevin R, Macdonald Timothy L
机构信息
Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, Charlottesville, VA 22904, USA.
出版信息
Bioorg Med Chem. 2008 Mar 1;16(5):2212-25. doi: 10.1016/j.bmc.2007.11.078. Epub 2007 Dec 4.
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 beta-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated alpha- and beta-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of beta-hydroxy phosphonates was also studied.
摘要
自分泌运动因子（ATX）因其溶血磷脂酶D活性可产生溶血磷脂酸（LPA），而成为一个颇具吸引力的药理学靶点。小分子阻断ATX产生LPA可能是一种潜在的抗癌化疗方法。在我们之前的研究中，我们已确定LPA的两种β-羟基膦酸酯类似物（化合物f17和f18）为ATX抑制剂。在这项工作中，我们研究了LPA的α-和β-取代膦酸酯类似物，并评估了它们的ATX抑制活性。我们还研究了β-羟基膦酸酯的立体化学。
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