methyl trans-4-[1-[[2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate | 1361414-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl trans-4-[1-[[2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate
• CAS: 1361414-57-4
• 化学式: C₃₁H₃₄FN₃O₅
• 分子量: 547.626
• InChiKey: JENUBOOPXUUGNE-MLCQCVOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  86.8
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl trans-4-[1-[[2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.0h， 以94%的产率得到trans-4-[1-[[2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid
  参考文献：
  名称：

  Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist

  摘要：

  For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido) phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse alpha(4) antibody (R1-2). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.045
• 作为产物：
  描述：

  methyl (4-amino-3-hydroxyphenyl)acetate 在 4-二甲氨基吡啶 、 硼酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 methyl trans-4-[1-[[2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate
  参考文献：
  名称：

  Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist

  摘要：

  For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido) phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse alpha(4) antibody (R1-2). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.045