4-{carboxy-[4-(1H-indol-3-yl)-piperidin-1-yl]-methyl}-piperidine-1-carboxylic acid tert-butyl ester | 881016-90-6

• 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: 4-{carboxy-[4-(1H-indol-3-yl)-piperidin-1-yl]-methyl}-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 2-[4-(1H-indol-3-yl)piperidin-1-yl]-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid
• CAS: 881016-90-6
• 化学式: C₂₅H₃₅N₃O₄
• 分子量: 441.571
• InChiKey: RODJIXPLYJNART-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-{carboxy-[4-(1H-indol-3-yl)-piperidin-1-yl]-methyl}-piperidine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 [4-(1H-indol-3-yl)-piperidin-1-yl]-piperidin-4-yl-acetic acid
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship and in Vivo Antiinflammatory Efficacy of Substituted Dipiperidines as CCR2 Antagonists

  摘要：

  A series of substituted dipiperidine compounds have been synthesized and identified as selective CCR2 antagonists. Combining the most favorable substituents led to the discovery of remarkably potent CCR2 antagonists displaying IC50 values in the nanomolar range. Compound 7a had outstanding selectivity over CCR1, CCR3, CCR4, CCR5, CCR6, CCR7, and CCR8 and showed excellent efficacy in adjuvant-induced arthritis model, collagen-induced arthritis model, and allergic asthma model.

  DOI：

  10.1021/jm070902b
• 作为产物：
  描述：

  a-溴-1-[(1,1-二甲基乙氧基)羰基]-4-哌啶乙酸 、 3-(4’-哌啶基)-1H-吲哚 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以27%的产率得到4-{carboxy-[4-(1H-indol-3-yl)-piperidin-1-yl]-methyl}-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Substituted dipiperidine CCR2 antagonists

  摘要：

  Formula (I)的替代二哌啶化合物或其盐、异构体、前药、代谢物或多型体，其为CCR2拮抗剂，可用于预防、治疗或改善需要的主体中的CCR2介导的炎症综合症、紊乱或疾病。

  公开号：

  US20060069123A1

文献信息

• Substituted dipiperidine CCR2 antagonists
  申请人：Xia Mingde

  公开号：US20060069123A1

  公开（公告）日：2006-03-30

  Substituted dipiperidine compounds of Formula (I) or a salt, isomer, prodrug, metabolite or polymorph thereof, which are CCR2 antagonists and are useful in preventing, treating or ameliorating CCR2 mediated inflammatory syndromes, disorders or diseases in a subject in need thereof.

  Formula (I)的替代二哌啶化合物或其盐、异构体、前药、代谢物或多型体，其为CCR2拮抗剂，可用于预防、治疗或改善需要的主体中的CCR2介导的炎症综合症、紊乱或疾病。
• Synthesis, Structure−Activity Relationship and in Vivo Antiinflammatory Efficacy of Substituted Dipiperidines as CCR2 Antagonists
  作者：Mingde Xia、Cuifen Hou、Duane E. DeMong、Scott R. Pollack、Meng Pan、James A. Brackley、Nareshkumar Jain、Chrissy Gerchak、Monica Singer、Ravi Malaviya、Michele Matheis、Gil Olini、Druie Cavender、Michael Wachter

  DOI：10.1021/jm070902b

  日期：2007.11.1

  A series of substituted dipiperidine compounds have been synthesized and identified as selective CCR2 antagonists. Combining the most favorable substituents led to the discovery of remarkably potent CCR2 antagonists displaying IC50 values in the nanomolar range. Compound 7a had outstanding selectivity over CCR1, CCR3, CCR4, CCR5, CCR6, CCR7, and CCR8 and showed excellent efficacy in adjuvant-induced arthritis model, collagen-induced arthritis model, and allergic asthma model.