| 2708226-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• CAS: 2708226-80-4
• 化学式: C₁₇H₁₆FN₃.2ClH
• 分子量: 354.25
• InChiKey: FUECRNDLKIHNRU-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  [4-(ethoxycarbonyl)bicyclo[2.2.1]hept-1-yl]acetic acid 、 在 N,N-二甲基甲酰胺 草酰氯 、 N,N-二异丙基乙胺 、 水 、 sodium hydroxide 、 盐酸 作用下， 以 二氯甲烷 、 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 以88 %的产率得到4-{2-[9-(4-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]-2-oxoethyl}bicyclo[2.2.1]heptane-1-carboxylic acid
  参考文献：
  名称：

  ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model

  摘要：

  Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chemistry effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (20), with good oral availability. To enhance the enzymatic ATX inhibitory activity, we designed several compounds by structurally comparing our hit compound with the endogenous ligand LPC. Further optimization to improve the pharmacokinetic profile and enhance the ATX inhibitory activity in human plasma resulted in the identification of ONO-8430506 (20), which enhanced the antitumor effect of paclitaxel in a breast cancer model.

  DOI：

  10.1021/acsmedchemlett.0c00200