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[2.2.2]octane-1-carboxylic acid | 1354804-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 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[2.2.2]octane-1-carboxylic acid
• 英文别名: 4-[2-[8-[(4-Fluorophenyl)methyl]-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),10,12-tetraen-5-yl]-2-oxoethyl]bicyclo[2.2.2]octane-1-carboxylic acid；4-[2-[8-[(4-fluorophenyl)methyl]-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),10,12-tetraen-5-yl]-2-oxoethyl]bicyclo[2.2.2]octane-1-carboxylic acid
• CAS: 1354804-83-3
• 化学式: C₂₈H₃₀FN₃O₃
• 分子量: 475.563
• InChiKey: OUQPEHGBQGSDPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  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[2.2.2]octane-1-carboxylic acid 、 联硼酸频那醇酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以65 %的产率得到methyl 4-(2-oxo-2-(9-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)-5,6,8,9-tetrahydro-7H-pyrrolo[2,3-b:5,4-c']dipyridin-7-yl)ethyl)bicyclo[2.2.2]octane-1-carboxylate
  参考文献：
  名称：

  [18F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX)

  摘要：

  DOI：

  10.1016/j.bmcl.2023.129345
• 作为产物：
  描述：

  4-methoxycarbonylcyclohexane-1-carboxylic acid 在 氯化亚砜 、 草酰氯 、 silver trifluoromethanesulfonate 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 正己烷 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 9.0h， 生成 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[2.2.2]octane-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

文献信息

• TETRAHYDROCARBOLINE DERIVATIVE
  申请人：Ohata Akira

  公开号：US20130109699A1

  公开（公告）日：2013-05-02

  An object of the present invention is to provide a drug having the inhibitory activity on ENPP2 which is a different target from that of the existing drug, as a medicament useful in a urinary excretion disorder patient for whom the existing drug has the insufficient effect. The present invention provides a compound represented by the general formula (I): (wherein definition of each group is as defined in the description) having the ENPP2 inhibitory activity, a salt thereof or a solvate thereof or a prodrug thereof, and an agent for preventing or treating urinary excretion disorder and/or improving symptoms thereof, containing them as an active ingredient.

  本发明的目的是提供一种药物，具有对ENPP2具有抑制活性，该活性与现有药物的靶点不同，作为一种对现有药物效果不足的尿液排泄障碍患者有用的药物。本发明提供了一种由通式（I）表示的化合物：（其中每个基团的定义如描述中所定义）具有ENPP2抑制活性，其盐或溶剂或前药，以及作为活性成分的含有它们的用于预防或治疗尿液排泄障碍和/或改善症状的药剂。
• US9006246B2
  申请人：——

  公开号：US9006246B2

  公开（公告）日：2015-04-14
• US9636330B2
  申请人：——

  公开号：US9636330B2

  公开（公告）日：2017-05-02
• US9974777B2
  申请人：——

  公开号：US9974777B2

  公开（公告）日：2018-05-22