2,5-dichloro-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)benzenesulfonamide | 1335250-86-6

• 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: 2,5-dichloro-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)benzenesulfonamide
• 英文别名: 2,5-dichloro-N-[(2,2-dimethylchromen-6-yl)methyl]-N-propan-2-ylbenzenesulfonamide
• CAS: 1335250-86-6
• 化学式: C₂₁H₂₃Cl₂NO₃S
• 分子量: 440.391
• InChiKey: VPTGVRIUIJTQRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 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 2,5-dichloro-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)benzenesulfonamide
  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

• 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
  作者：Jiyoung Mun、Adnan Abdul Jabbar、Narra Sarojini Devi、Yuan Liu、Erwin G. Van Meir、Mark M. Goodman

  DOI：10.1016/j.bmc.2012.04.064

  日期：2012.7

  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.