N-(1-hexylpiperidin-4-yl)xanthene-9-carboxamide | 202795-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-(1-hexylpiperidin-4-yl)xanthene-9-carboxamide
• 英文别名: N-(1-hexylpiperidin-4-yl)-9H-xanthene-9-carboxamide
• CAS: 202795-89-9
• 化学式: C₂₅H₃₂N₂O₂
• 分子量: 392.541
• InChiKey: ZSBQWSHGCMDNMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 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：

  N-(1-hexylpiperidin-4-yl)xanthene-9-carboxamide 生成 1-hexyl-1-methyl-4-(xanthene-9-carboxamido)piperidinium iodide
  参考文献：
  名称：

  Chemokine receptor antagonists

  摘要：

  本发明涉及一般式的化合物：##STR1##其中R.sup.1和R.sup.2中的每一个可以相同也可以不同，例如是氢原子、卤素原子或低碳基团，X是氧原子、硫原子或CH，Y是CH或氮原子，A是例如1-取代-4-哌啶基团，其药学上可接受的盐，其药学上可接受的阴离子交换产物或其水合物。本发明的化合物具有趋化因子受体拮抗作用，因此它们可用作治疗与趋化因子相关的各种疾病的药剂，如急性炎症性疾病、慢性炎症性疾病、获得性免疫缺陷综合症、癌症、缺血再灌注障碍和/或动脉粥样硬化。

  公开号：

  US06140338A1
• 作为产物：
  描述：

  N-(1-tert-butyloxycarbonylpiperidin-4-yl)xanthene-9-carboxamide 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 N-(1-hexylpiperidin-4-yl)xanthene-9-carboxamide
  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

• CHEMOKINE RECEPTOR ANTAGONISTS
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0916668A1

  公开（公告）日：1999-05-19

  The present invention relates to a compound of the general formula: wherein each of R1 and R2 which may be the same or different, is e.g. a hydrogen atom, a halogen atom or a lower alkyl group, X is an oxygen atom, a sulfur atom or CH, Y is CH or a nitrogen atom, and A is e.g. a 1-substituted-4-piperidinyl group, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable anion-exchange product thereof or a hydrate thereof. The compounds of the present invention have chemokine receptor antagonism, and thus they are useful as treating agents for various diseases relating to chemokine, such as acute inflammatory diseases, chronic inflammatory diseases, acquired immune deficiency syndrome, cancer, ischemic reflow disorder and/or arteriosclerosis.

  本发明涉及通式如下的化合物： 其中R1和R2可以相同或不同，每个R1和R2例如是氢原子、卤素原子或低级烷基，X是氧原子、硫原子或CH，Y是CH或氮原子，A例如是1-取代-4-哌啶基、其药学上可接受的盐、其药学上可接受的阴离子交换产物或其水合物。 本发明的化合物具有趋化因子受体拮抗作用，因此可作为治疗与趋化因子有关的各种疾病的药物，如急性炎症性疾病、慢性炎症性疾病、获得性免疫缺陷综合征、癌症、缺血性回流障碍和/或动脉硬化。
• US6140338A
  申请人：——

  公开号：US6140338A

  公开（公告）日：2000-10-31
• 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.
• Chemokine receptor antagonists
  申请人：Banyu Pharmaceutical, Co., Ltd.

  公开号：US06140338A1

  公开（公告）日：2000-10-31

  The present invention relates to a compound of the general formula: ##STR1## wherein each of R.sup.1 and R.sup.2 which may be the same or different, is e.g. a hydrogen atom, a halogen atom or a lower alkyl group, X is an oxygen atom, a sulfur atom or CH, Y is CH or a nitrogen atom, and A is e.g. a 1-substituted-4-piperidinyl group, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable anion-exchange product thereof or a hydrate thereof. The compounds of the present invention have chemokine receptor antagonism, and thus they are useful as treating agents for various diseases relating to chemokine, such as acute inflammatory diseases, chronic inflammatory diseases, acquired immune deficiency syndrome, cancer, ischemic reflow disorder and/or arteriosclerosis.

  本发明涉及一般式的化合物：##STR1##其中R.sup.1和R.sup.2中的每一个可以相同也可以不同，例如是氢原子、卤素原子或低碳基团，X是氧原子、硫原子或CH，Y是CH或氮原子，A是例如1-取代-4-哌啶基团，其药学上可接受的盐，其药学上可接受的阴离子交换产物或其水合物。本发明的化合物具有趋化因子受体拮抗作用，因此它们可用作治疗与趋化因子相关的各种疾病的药剂，如急性炎症性疾病、慢性炎症性疾病、获得性免疫缺陷综合症、癌症、缺血再灌注障碍和/或动脉粥样硬化。