ethyl 1-[1-(tert-butoxycarbonyl)-(4S)-fluoro-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetate | 441714-17-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 1-[1-(tert-butoxycarbonyl)-(4S)-fluoro-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetate
• 英文别名: tert-butyl (2S,4S)-2-[4-(2-ethoxy-2-oxoethyl)piperidine-1-carbonyl]-4-fluoropyrrolidine-1-carboxylate
• CAS: 441714-17-6
• 化学式: C₁₉H₃₁FN₂O₅
• 分子量: 386.464
• InChiKey: MOBKXPGFXPSBGC-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 1-[1-(tert-butoxycarbonyl)-(4S)-fluoro-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以100%的产率得到ethyl 1-[(4S)-fluoro-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetate
  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：

  4-哌啶乙酸乙酯 、 (2S,4S)-N-Boc-顺式-4-氟-L-脯氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以32%的产率得到ethyl 1-[1-(tert-butoxycarbonyl)-(4S)-fluoro-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetate
  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

• VLA-4 INHIBITORS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1346982B1

  公开（公告）日：2011-09-14
• US7157487B2
  申请人：——

  公开号：US7157487B2

  公开（公告）日：2007-01-02