ethyl 1-bromomethyl-4,4-ethylenedioxycyclohexanecarboxylate | 159329-32-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 1-bromomethyl-4,4-ethylenedioxycyclohexanecarboxylate
• 英文别名: ethyl 8-(bromomethyl)-1,4-dioxaspiro[4.5]decane-8-carboxylate；8-Bromomethyl-1,4-dioxa-spiro[4.5]decane-8-carboxylic acid ethyl ester
• CAS: 159329-32-5
• 化学式: C₁₂H₁₉BrO₄
• 分子量: 307.184
• InChiKey: NIOZIGDAXFKNBK-UHFFFAOYSA-N

物化性质

• 沸点：
  360.2±42.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-bromomethyl-4,4-ethylenedioxycyclohexanecarboxylate 在 盐酸 、 草酰氯 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 丙酮 、 甲苯 、 mineral oil 为溶剂， 反应 8.33h， 生成 4-{2-[9-(2,4-difluorobenzyl)-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
• 作为产物：
  描述：

  1,4-二噁螺[4.5]癸烷-8-羧酸乙酯 以86%的产率得到
  参考文献：
  名称：

  Della Ernest W., Knill Andrew M., Austal. J. Chem, 47 (1994) N 10, S 1833-1841

  摘要：

  DOI：

文献信息

• Synthesis of Bridgehead Substituted Bicyclo[2.2.1]Heptanes. Radical Cyclization of an Oxime Ether and an α,β-Unsaturated Ester
  作者：EW Della、AM Knill

  DOI：10.1071/ch9941833

  日期：——

  The synthesis of bicyclo[2.2.1]heptanes with useful functionality at each bridgehead is achieved by radical cyclization of appropriately substituted 4-methylene- and 4-benzyloxyimino- cyclohexylmethyl radicals. The latter process, for example, leads to a bridgehead amine. Optimum yields are achieved when the reactions are conducted at 110� with slow addition of tributyltin hydride; under these conditions, the uncyclized isomer is either not detected, or formed in very small quantity. Production of a mixture of five- and six-membered cycloalkanones from similar treatment of the analogous 4-oxocyclohexylmethyl radicals reveals that the reaction is medicated by the corresponding 1-norbornyloxy radical.

  通过对适当取代的 4-亚甲基和 4-苄氧基亚氨基环己基甲基进行自由基环化，可以合成在每个桥头都具有有用官能团的双环[2.2.1]庚烷。例如，后一过程会产生桥头胺。当反应在 110� 温度下进行并缓慢加入氢化三丁基锡时，可获得最佳产率；在这些条件下，未环化的异构体要么检测不到，要么形成的数量极少。通过对类似的 4-oxocyclohexylmethyl 自由基进行类似处理，生成五元和六元环烷酮混合物，结果表明该反应受相应的 1-正硼氧基自由基的影响。
• Hydroxamic and carboxylic acid derivatives
  申请人：Darwin Discovery Ltd.

  公开号：US06503910B1

  公开（公告）日：2003-01-07

  Compounds of the formula (B)2N—X—(CH2)n—CR1R2—CO—Y  (I) have therapeutic utility as inhibitors of metalloproteinases etc.

  化合物(B)2N—X—(CH2)n—CR1R2—CO—Y  (I)的公式，具有作为金属蛋白酶抑制剂等治疗用途。
• Della Ernest W., Knill Andrew M., Austal. J. Chem, 47 (1994) N 10, S 1833-1841
  作者：Della Ernest W., Knill Andrew M.

  DOI：——

  日期：——
• HYDROXAMIC AND CARBOXYLIC ACID DERIVATIVES
  申请人：Darwin Discovery Limited

  公开号：EP1177183A1

  公开（公告）日：2002-02-06
• US6503910B1
  申请人：——

  公开号：US6503910B1

  公开（公告）日：2003-01-07