methyl 2-{4-[3-(4-fluorophenoxy)-5-nitrophenoxy]phenyl}-2-methylpropanoate | 1428901-07-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-{4-[3-(4-fluorophenoxy)-5-nitrophenoxy]phenyl}-2-methylpropanoate
• 英文别名: Methyl 2-(4-(3-(4-fluorophenoxy)-5-nitrophenoxy)phenyl)-2-methylpropanoate；methyl 2-[4-[3-(4-fluorophenoxy)-5-nitrophenoxy]phenyl]-2-methylpropanoate
• CAS: 1428901-07-8
• 化学式: C₂₃H₂₀FNO₆
• 分子量: 425.413
• InChiKey: BBYQGNHHDJNSDY-UHFFFAOYSA-N

物化性质

• 沸点：
  499.7±45.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-{4-[3-(4-fluorophenoxy)-5-nitrophenoxy]phenyl}-2-methylpropanoate 在 5%-palladium/activated carbon 、 水 、 氢气 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基乙酰胺 、 乙酸乙酯 为溶剂， 生成 2-{4-[3-(4-fluorophenoxy)-5-{[(3-hydroxy-3-isobutyl-1-pyrrolidinyl)carbonyl]amino}phenoxy]phenyl}-2-methylpropanoic acid
  参考文献：
  名称：

  Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives

  摘要：

  The structure of the S1P(2) antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure. Based on these changes, the pyrrolidine derivative 16 was identified as a suitable candidate compound and showed excellent pharmacokinetic profiles in rat and dog, while maintaining high levels of potency and selective antagonistic activity toward S1P(2). (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.031
• 作为产物：
  描述：

  2-（4-（苄氧基）苯基）-2-甲基丙酸甲酯 在 potassium phosphate 、 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 生成 methyl 2-{4-[3-(4-fluorophenoxy)-5-nitrophenoxy]phenyl}-2-methylpropanoate
  参考文献：
  名称：

  Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives

  摘要：

  The structure of the S1P(2) antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure. Based on these changes, the pyrrolidine derivative 16 was identified as a suitable candidate compound and showed excellent pharmacokinetic profiles in rat and dog, while maintaining high levels of potency and selective antagonistic activity toward S1P(2). (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.031

文献信息

• Phenyl derivative
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US08975409B2

  公开（公告）日：2015-03-10

  The compound represented by the formula (I-1): wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1P2 antagonistic activity. The compound may therefore be used as a therapeutic agent for S1P2-mediated diseases such as diseases resulting from vascular constriction, fibrosis and respiratory diseases.

  化合物的化学式为（I-1）：其中所有符号的含义与说明书中描述的相同，具有两个环状基团，特别是在特定的取代位置上有苯氧基团，因此具有高人类S1P2拮抗活性。因此，该化合物可用作S1P2介导疾病的治疗剂，例如由血管收缩、纤维化和呼吸系统疾病引起的疾病。
• PHENYL DERIVATIVE
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP2762466B1

  公开（公告）日：2017-06-21
• US8975409B2
  申请人：——

  公开号：US8975409B2

  公开（公告）日：2015-03-10
• US9340499B2
  申请人：——

  公开号：US9340499B2

  公开（公告）日：2016-05-17
• US9820980B2
  申请人：——

  公开号：US9820980B2

  公开（公告）日：2017-11-21