N-(3-(((1-acetyl-1H-indol-3-yl)methyl)amino)propyl)-5-phenylisoxazole-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(3-(((1-acetyl-1H-indol-3-yl)methyl)amino)propyl)-5-phenylisoxazole-3-carboxamide
• 英文别名: N-[3-[(1-acetylindol-3-yl)methylamino]propyl]-5-phenyl-1,2-oxazole-3-carboxamide
• 化学式: C₂₄H₂₄N₄O₃
• 分子量: 416.48
• InChiKey: HMYITRIHRHWDTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl (3-(5-phenylisoxazole-3-carboxamido)propyl)carbamate 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 N-(3-(((1-acetyl-1H-indol-3-yl)methyl)amino)propyl)-5-phenylisoxazole-3-carboxamide
  参考文献：
  名称：

  Optimization of a small molecule probe that restores e-cadherin expression

  摘要：

  E-cadherin is a ubiquitous trans-membrane protein that has important functions in cellular contacts and has been shown to play a role in the epithelial mesenchymal transition. We have previously reported the use of an HTS screen to identify compounds that are capable of restoring e-cadherin in cancer cells. Here, we report the additional medicinal chemistry optimization of these molecules, resulting in new molecules that restore e-cadherin expression at low micromolar concentrations. Further, we report preliminary pharmacokinetic data on a compound, ML327, that can be used as a probe of e-cadherin restoration. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.104

文献信息

• ISOXAZOLE ANALOGS AS MEDIATORS OF TRANSCRIPTIONAL INDUCTION OF E-CADHERIN
  申请人：Vanderbilt University

  公开号：US20160052896A1

  公开（公告）日：2016-02-25

  In one aspect, the invention relates to N-((arylamino)alkyl)-5-arylisoxazole-3-carboxamide analogs, derivatives thereof, and related compounds, which are useful as mediators of transcriptional induction of E-cadherin; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with E-cadherin activity using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及N-((芳基氨基)烷基)-5-芳基异噁唑-3-羧酰胺类似物，其衍生物和相关化合物，这些化合物可用作E-钙粘蛋白的转录诱导介质；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与E-钙粘蛋白活性相关的疾病的方法。本摘要旨在作为在特定领域搜索的扫描工具，并不意味着对本发明的限制。
• US9505729B2
  申请人：——

  公开号：US9505729B2

  公开（公告）日：2016-11-29
• Optimization of a small molecule probe that restores e-cadherin expression
  作者：John T. Brogan、Sydney L. Stoops、Suzanne Brady、Hanbing An、Connie Weaver、J. Scott Daniels、R. Daniel Beauchamp、Craig W. Lindsley、Alex G. Waterson

  DOI：10.1016/j.bmcl.2015.07.104

  日期：2015.10

  E-cadherin is a ubiquitous trans-membrane protein that has important functions in cellular contacts and has been shown to play a role in the epithelial mesenchymal transition. We have previously reported the use of an HTS screen to identify compounds that are capable of restoring e-cadherin in cancer cells. Here, we report the additional medicinal chemistry optimization of these molecules, resulting in new molecules that restore e-cadherin expression at low micromolar concentrations. Further, we report preliminary pharmacokinetic data on a compound, ML327, that can be used as a probe of e-cadherin restoration. (C) 2015 Elsevier Ltd. All rights reserved.