N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)oxazole-4-carboxamide | 1186295-70-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)oxazole-4-carboxamide
• 英文别名: ND-008505；JAS-I-190；N-[[1-[(3-phenoxyphenyl)methyl]triazol-4-yl]methyl]-1,3-oxazole-4-carboxamide
• CAS: 1186295-70-4
• 化学式: C₂₀H₁₇N₅O₃
• 分子量: 375.387
• InChiKey: QIOZVDOEQJIMBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(prop-2-ynyl)oxazole-4-carboxamide 、 1-(叠氮甲基)-3-苯氧基苯 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 96.0h， 生成 N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)oxazole-4-carboxamide
  参考文献：
  名称：

  N-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide as a New Scaffold that Provides Rapid Access to Antimicrotubule Agents: Synthesis and Evaluation of Antiproliferative Activity Against Select Cancer Cell Lines

  摘要：

  A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC50 of 46 nM against MCF-7 human breast tumor cells. Structure activity relationship (SA R) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G(2)/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.

  DOI：

  10.1021/jm1000979

文献信息

• ANTI-CANCER COMPOUNDS, SYNTHESIS THEREOF, AND METHODS OF USING SAME
  申请人：Miller Marvin J.

  公开号：US20110021574A1

  公开（公告）日：2011-01-27

  Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to anti-cancer compounds, synthesis thereof, and methods of using same. Disclosed herein are various heterocyclic compounds and methods of using the novel anti-cancer compounds to inhibit the growth of a cancer cell, for instance a leukemia, non-small cell lung, central nervous system (CNS), skin, ovarian, renal, prostate, breast, or colon cancer cell. Other embodiments include methods of treating cancer in a subject, such as using the disclosed heterocyclic anti-cancer agents.
• US8268874B2
  申请人：——

  公开号：US8268874B2

  公开（公告）日：2012-09-18
• US8729270B2
  申请人：——

  公开号：US8729270B2

  公开（公告）日：2014-05-20
• <i>N</i>-((1-Benzyl-1<i>H</i>-1,2,3-triazol-4-yl)methyl)arylamide as a New Scaffold that Provides Rapid Access to Antimicrotubule Agents: Synthesis and Evaluation of Antiproliferative Activity Against Select Cancer Cell Lines
  作者：Jonathan A. Stefely、Rahul Palchaudhuri、Patricia A. Miller、Rebecca J. Peterson、Garrett C. Moraski、Paul J. Hergenrother、Marvin J. Miller

  DOI：10.1021/jm1000979

  日期：2010.4.22

  A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC50 of 46 nM against MCF-7 human breast tumor cells. Structure activity relationship (SA R) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G(2)/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.