1-[(2R,3R)-2-[[2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl(methyl)amino]methyl]-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-3-isoquinolin-1-ylurea | 1434081-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-[(2R,3R)-2-[[2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl(methyl)amino]methyl]-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-3-isoquinolin-1-ylurea
• CAS: 1434081-60-3
• 化学式: C₃₄H₃₇N₅O₈S
• 分子量: 675.762
• InChiKey: BCFDKLQIHKJIHD-DGIFUFQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  48
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  168
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二氧-6-磺酰氯 在 2,6-二甲基吡啶 、 palladium 10% on activated carbon 、 氢气 、 1,8-双二甲氨基萘 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 23.75h， 生成 1-[(2R,3R)-2-[[2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl(methyl)amino]methyl]-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-6-oxo-3,4-dihydro-2H-1,5-benzoxazocin-10-yl]-3-isoquinolin-1-ylurea
  参考文献：
  名称：

  Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction in β-Cells with Improved Aqueous Solubility

  摘要：

  We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced beta-cell apoptosis. Herein, we report the synthesis and biological evaluation of I and analogues with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogues with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that 1 and analogues inhibit STAT1 signal transduction induced by IFN-gamma.

  DOI：

  10.1021/jm400397x

文献信息

• Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction in β-Cells with Improved Aqueous Solubility
  作者：Stephen S. Scully、Alicia J. Tang、Morten Lundh、Carrie M. Mosher、Kedar M. Perkins、Bridget K. Wagner

  DOI：10.1021/jm400397x

  日期：2013.5.23

  We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced beta-cell apoptosis. Herein, we report the synthesis and biological evaluation of I and analogues with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogues with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that 1 and analogues inhibit STAT1 signal transduction induced by IFN-gamma.