1,4-Piperidinedicarboxylic acid,3-[[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]amino]carbonyl]-,bis(1,1-dimethylethyl) ester, (3R,4S)- | 654647-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,4-Piperidinedicarboxylic acid,3-[[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]amino]carbonyl]-,bis(1,1-dimethylethyl) ester, (3R,4S)-
• 英文别名: (3R,4S)-3-[4-(2-Methyl-quinolin-4-ylmethoxy)-phenylcarbamoyl]-piperidine-1,4-dicarboxylic acid di-tert-butyl ester
• CAS: 654647-09-3
• 化学式: C₃₃H₄₁N₃O₆
• 分子量: 575.705
• InChiKey: NRYLCEACTKGRAV-SVBPBHIXSA-N

物化性质

• 沸点：
  723.1±60.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.28
• 重原子数：
  42.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  107.06
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1,4-Piperidinedicarboxylic acid,3-[[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]amino]carbonyl]-,bis(1,1-dimethylethyl) ester, (3R,4S)- 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到
  参考文献：
  名称：

  Rational design, synthesis and structure–activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: lead optimization

  摘要：

  Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-{[4-(4-quinolinyloxymethyl)anilinyl]carbonyl}-1-cyclo-hexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide] exhibited an IC50 value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.057
• 作为产物：
  描述：

  [4-(2-methylquinolin-4-ylmethoxy)phenyl]-carbamic acid tert-butyl ester 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,4-Piperidinedicarboxylic acid,3-[[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]amino]carbonyl]-,bis(1,1-dimethylethyl) ester, (3R,4S)-
  参考文献：
  名称：

  Rational design, synthesis and structure–activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: lead optimization

  摘要：

  Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-{[4-(4-quinolinyloxymethyl)anilinyl]carbonyl}-1-cyclo-hexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide] exhibited an IC50 value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.057