N-(7-nitro-3,4-dihydro-2H-chromen-6-yl)acetamide | 50603-79-7

• 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-(7-nitro-3,4-dihydro-2H-chromen-6-yl)acetamide
• 英文别名: N-(7-nitrochroman-6-yl)acetamide；N-(7-nitro-chroman-6-yl)-acetamide；6-Acetamido-7-nitrochroman
• CAS: 50603-79-7
• 化学式: C₁₁H₁₂N₂O₄
• 分子量: 236.227
• InChiKey: DDRJACWVUYHXHI-UHFFFAOYSA-N

物化性质

• 熔点：
  141-143 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  452.9±45.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(7-nitro-3,4-dihydro-2H-chromen-6-yl)acetamide 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 7.25h， 生成 chroman-7-amine
  参考文献：
  名称：

  Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

  摘要：

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.005
• 作为产物：
  描述：

  3,4-二2H-1-苯并吡喃-6-胺 在 吡啶 、 硝酸 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.5h， 生成 N-(7-nitro-3,4-dihydro-2H-chromen-6-yl)acetamide
  参考文献：
  名称：

  Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

  摘要：

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.005

文献信息

• Tricyclic 1,2,4-triazine oxides and compositions for therapeutic use in cancer treatments
  申请人：Auckland Uniservices Limited

  公开号：US07989451B2

  公开（公告）日：2011-08-02

  The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及新型三环1,2,4-三嗪-1-氧化物和新型三环1,2,4-三嗪-1,4-二氧化物的公式I以及相关类似物，涉及它们的制备，以及它们作为缺氧选择性药物和放射增敏剂用于癌症治疗，无论是单独使用还是与放射治疗和/或其他抗癌药物联合使用。
• Tricyclic 1,2,4-Triazine Oxides and Compositions for Therapeutic Use in Cancer Treatments
  申请人：Hay Michael Patrick

  公开号：US20090186886A1

  公开（公告）日：2009-07-23

  The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及新型三环1,2,4-三嗪-1-氧化物和新型三环1,2,4-三嗪-1,4-二氧化物的公式I以及相关类似物，它们的制备以及它们作为低氧选择性药物和放射增敏剂用于癌症治疗，可以单独使用或与放射线和/或其他抗癌药物联合使用。
• WO2006/104406
  申请人：——

  公开号：——

  公开（公告）日：——
• Tricyclic [1,2,4]Triazine 1,4-Dioxides As Hypoxia Selective Cytotoxins
  作者：Michael P. Hay、Kevin O. Hicks、Karin Pchalek、Ho H. Lee、Adrian Blaser、Frederik B. Pruijn、Robert F. Anderson、Sujata S. Shinde、William R. Wilson、William A. Denny

  DOI：10.1021/jm800967h

  日期：2008.11.13

  A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing Saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined 7 using pharmacokinetic/phamacodynamic model predictions of the in vivo hypoxic potency (AUC(req)) and selectivity (HCD) with 12 TTO analogues predicted to be active in Vivo, Subject to the achievement of adequate plasma pharmacokinetics.
• TRICYCLIC 1,2,4-TRIAZINE OXIDES AND COMPOSITIONS THEREFROM FOR THERAPEUTIC USE IN CANCER TREATMENTS
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP1866292B1

  公开（公告）日：2010-12-15