3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide | 927823-01-6

• 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: 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide
• 英文别名: N-((2,2-dimethyl-2H-chromen-6-yl)methyl)-3,4-dimethoxy-N-phenylbenzenesulfonamide；KCN1；3,4-dimethoxy-N-((2,2-dimethyl-2H-chromen-6-yl)methyl)-N-phenylbenzenesulfonamide；N-[(2,2-dimethylchromen-6-yl)methyl]-3,4-dimethoxy-N-phenylbenzenesulfonamide
• CAS: 927823-01-6
• 化学式: C₂₆H₂₇NO₅S
• 分子量: 465.57
• InChiKey: IPZJNJPAVPZHJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide 在 potassium carbonate 、 一水合肼 、 苯硫酚 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 4-(4-aminobutoxy)-N-((2,2-dimethyl-2H-chromen-6-yl)methyl)-3-methoxy-N-phenylbenzenesulfonamide
  参考文献：
  名称：

  抗癌芳基磺酰胺与 p300 转录辅因子相互作用的结合模型

  摘要：

  缺氧诱导因子 (HIF) 是激活多种基因产物表达并促进肿瘤适应缺氧环境的转录因子。为了变得具有转录活性，HIF 与辅因子 p300 或 CBP 相关联。以前，我们发现芳基磺酰胺可以在生物测定中拮抗 HIF 转录，阻断 p300/HIF-1α 相互作用，并在几种动物模型中发挥有效的抗癌活性。在目前的工作中，KCN1-珠亲和下拉，14C 标记的 KCN1 结合和 KCN1 表面等离子体共振测量为 KCN1 可以与 p300 的 CH1 结构域结合并可能阻止 p300/HIF-1α 组装的机制提供初步支持。使用先前报道的 p300/HIF-1α 复合物的 NMR 结构，我们已经确定了 p300-CH1 域中的潜在结合位点。结合 IC 50值的双位点结合模型允许建立适度的基于 ROC 的富集并为未来的模拟合成创建指南。

  DOI：

  10.1021/ml300042k
• 作为产物：
  描述：

  4-((2-methylbut-3-yn-2-yl)oxy)benzaldehyde 在 N-甲基吡咯烷酮 、 二异丁基氢化铝 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 8.0h， 生成 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide
  参考文献：
  名称：

  Structure–activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule hypoxia inducible factor-1 (HIF-1) pathway inhibitor and anti-cancer agent

  摘要：

  We have discovered that 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzene-sulfonamide, a novel small molecule HIF-1 pathway inhibitor, can antagonize tumor growth in animal models of cancer, but the treatment necessitates its delivery in a formulation, due to poor water solubility (<15 mu g/mL; pH 7.4), evidencing that the chemotype needs further exploration of its amenability to additional chemical modifications for ultimate optimization of function and pharmacology.As a first step towards this goal we investigated the structure-activity relationships of 15 lipophilic 2, 2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide to find out strategies of modification. A 3,4-dimethoxybenzenesulfonyl group in region 1 showed the strongest inhibition among five arylsulfonyl groups tested. The presence of propan-2-amine in region 2 conferred the strongest inhibitory effect of the compound on HIF-1 activated transcription in a reporter assay. These findings are important as they help define the structural motifs where the 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide can be chemically modified to improve its pharmacological properties towards development as a cancer therapeutic. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.064

文献信息

• HYPOXIA INDUCIBLE FACTOR-1 PATHWAY INHIBITORS AND USES AS ANTICANCER AND IMAGING AGENTS
  申请人：EMORY UNIVERSITY

  公开号：US20130164218A1

  公开（公告）日：2013-06-27

  This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

  本公开涉及缺氧诱导因子-1通路抑制剂及其作为抗癌和成像剂的用途。在某些实施方式中，本公开考虑了在此披露的化合物和药物组成物。
• INHIBITORS OF HIF AND ANGIOGENESIS
  申请人：Van Meir Erwin G.

  公开号：US20130116275A1

  公开（公告）日：2013-05-09

  Inhibitors of the Hypoxia Inducible Factor (HIF) and angiogenesis and their methods of use including the treatment of cancer, hypoxia related pathologies, disorders leading to ischemia, for example stroke and ischemic heart disease, and non-cancerous angiogenic diseases are provided.

  本发明提供了针对缺氧诱导因子（HIF）和血管生成的抑制剂及其使用方法，包括用于治疗癌症、与缺氧相关的病理学、导致缺血的疾病（例如中风和缺血性心脏病）以及非癌性血管生成性疾病的治疗。
• Methods and compositions for managing vascular conditions using miR-483 mimics and HIF1alpha pathway inhibitors
  申请人：Emory University

  公开号：US11225660B2

  公开（公告）日：2022-01-18

  This disclosure relates to the use of miRNA-483 and its target genes, UBE2C, pVHL and HIF1alpha, in managing the treatment of cardiovascular and inflammatory diseases. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a miR-483 mimic and/or an HIF inhibitor and a pharmaceutically acceptable excipient for use in treating or preventing a vascular disease or condition. In certain embodiments, the miR-483 mimic is a double stranded nucleobase polymer or an expression vector that expresses mature human miR-483-5p and miR-483-3p sequences or operable fragments and variants.

  本公开涉及 miRNA-483 及其靶基因 UBE2C、pVHL 和 HIF1alpha 在治疗心血管疾病和炎症性疾病中的应用。在某些实施方案中，本公开涉及药物组合物，该组合物包含用于治疗或预防血管疾病或病症的 miR-483 模拟物和/或 HIF 抑制剂和药学上可接受的赋形剂。在某些实施方案中，miR-483模拟物是双链核碱基聚合物或表达成熟人miR-483-5p和miR-483-3p序列或可操作片段和变体的表达载体。
• WO2007/25169
  申请人：——

  公开号：——

  公开（公告）日：——
• Methods and Compositions for Managing Vascular Conditions Using miR-483 Mimics and HIF1alpha Pathway Inhibitors
  申请人：Emory University

  公开号：US20190112603A1

  公开（公告）日：2019-04-18

  This disclosure relates to the use of miRNA-483 and its target genes, UBE2C, pVHL and HIF1alpha, in managing the treatment of cardiovascular and inflammatory diseases. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a miR-483 mimic and/or an HIF inhibitor and a pharmaceutically acceptable excipient for use in treating or preventing a vascular disease or condition. In certain embodiments, the miR-483 mimic is a double stranded nucleobase polymer or an expression vector that expresses mature human miR-483-5p and miR-483-3p sequences or operable fragments and variants.