4-tert-butoxycarbonylamino-1-(1-cyclooctenylmethyl)piperidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-tert-butoxycarbonylamino-1-(1-cyclooctenylmethyl)piperidine
• 英文别名: [1-((E)-1-Cyclooct-1-enyl)methyl-piperidin-4-yl]-carbamic acid tert-butyl ester；tert-butyl N-[1-[[(1E)-cycloocten-1-yl]methyl]piperidin-4-yl]carbamate
• 化学式: C₁₉H₃₄N₂O₂
• 分子量: 322.491
• InChiKey: BBPVOCBYJROQCF-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-tert-butoxycarbonylamino-1-(1-cyclooctenylmethyl)piperidine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以96%的产率得到4-amino-1-(cyclooctenylmethyl)piperidine
  参考文献：
  名称：

  Design, Synthesis, and Discovery of a Novel CCR1 Antagonist

  摘要：

  The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of I-125-MIP-1 alpha. binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide la as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.

  DOI：

  10.1021/jm0004244
• 作为产物：
  描述：

  cyclooctanone p-tolylsulfonylhydrazone 在 正丁基锂 、 四甲基乙二胺 、 三乙酰氧基硼氢化钠 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 22.5h， 生成 4-tert-butoxycarbonylamino-1-(1-cyclooctenylmethyl)piperidine
  参考文献：
  名称：

  Design, Synthesis, and Discovery of a Novel CCR1 Antagonist

  摘要：

  The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of I-125-MIP-1 alpha. binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide la as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.

  DOI：

  10.1021/jm0004244

文献信息

• Design, Synthesis, and Discovery of a Novel CCR1 Antagonist
  作者：Akira Naya、Yufu Sagara、Kenji Ohwaki、Toshihiko Saeki、Daisuke Ichikawa、Yoshikazu Iwasawa、Kazuhito Noguchi、Norikazu Ohtake

  DOI：10.1021/jm0004244

  日期：2001.4.1

  The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of I-125-MIP-1 alpha. binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide la as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.