methyl trans-4-[1-benzyloxycarbonyl-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate | 1138432-16-2

• 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 trans-4-[1-benzyloxycarbonyl-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate
• 英文别名: benzyl (2S,4S)-4-fluoro-2-[(4-methoxycarbonylcyclohexyl)oxymethyl]pyrrolidine-1-carboxylate
• CAS: 1138432-16-2
• 化学式: C₂₁H₂₈FNO₅
• 分子量: 393.455
• InChiKey: YVSAXPJHSIAUPH-YBXZHIRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl trans-4-[1-benzyloxycarbonyl-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 在 palladium(II) hydroxide/carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 以97%的产率得到methyl 4-[(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate
  参考文献：
  名称：

  A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid

  摘要：

  During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-( 2- methylphenylamino) benzoxazole moiety which mimics the diphenylurea structure. However, this modi. cation resulted in a significant decrease ( 3, IC(50) = 19 nM) in VLA-4 inhibitory activity compared to 1 ( IC(50) = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC(50) = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties ( CL = 3.3ml/min/ kg, F = 51%) in rats. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.026
• 作为产物：
  描述：

  氯甲酸苄酯 、 methyl 4-[(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 在 碳酸氢钠 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.5h， 以61%的产率得到methyl cis-4-[1-benzyloxycarbonyl-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate
  参考文献：
  名称：

  A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid

  摘要：

  During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-( 2- methylphenylamino) benzoxazole moiety which mimics the diphenylurea structure. However, this modi. cation resulted in a significant decrease ( 3, IC(50) = 19 nM) in VLA-4 inhibitory activity compared to 1 ( IC(50) = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC(50) = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties ( CL = 3.3ml/min/ kg, F = 51%) in rats. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.026

文献信息

• US7157487B2
  申请人：——

  公开号：US7157487B2

  公开（公告）日：2007-01-02