3,3,3',3'-tetramethyl-1,1'-spirobi(indan)-5,5',6,6'-tetrol tetrasulfate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 英文名称: 3,3,3',3'-tetramethyl-1,1'-spirobi(indan)-5,5',6,6'-tetrol tetrasulfate
• 英文别名: (1,1,1',1'-tetramethyl-5',6,6'-trisulfooxy-3,3'-spirobi[2H-indene]-5-yl) hydrogen sulfate
• 化学式: C₂₁H₂₄O₁₆S₄
• 分子量: 660.676
• InChiKey: KABGKBROZNXJSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  288
• 氢给体数：
  4
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  5,5',6,6'-四羟基-3,3,3',3'-四甲基-1,1'-螺旋联吲哚 在 吡啶 、 氯磺酸 作用下， 生成 3,3,3',3'-tetramethyl-1,1'-spirobi(indan)-5,5',6,6'-tetrol tetrasulfate
  参考文献：
  名称：

  A New Class of HIV-1 Integrase Inhibitors:  The 3,3,3‘,3‘-Tetramethyl-1,1‘-spirobi(indan)-5,5‘,6,6‘-tetrol Family

  摘要：

  Integration is a required step in HIV replication, but as yet no inhibitors of the integration step have been developed for clinical use. Many inhibitors have been identified that are active against purified viral-encoded integrase protein; of these many contain a catechol moiety. Though this substructure contributes potency in inhibitors, it is associated with toxicity and so the utility of catechol-containing inhibitors has been questioned. We have synthesized and tested a systematic series of derivatives of a catechol-containing inhibitor (1) with the goal of identifying catechol isosteres that support inhibition. We find that different patterns of substitution on the aromatic ring suffice for inhibition when Mn2+ is used as a cofactor. Importantly, the efficiency is different when Mg2+, the more likely in vivo cofactor, is used. These data emphasize the importance of assays with Mg2+ and offer new catechol isosteres for use in integrase inhibitors.

  DOI：

  10.1021/jm990600c

文献信息

• A New Class of HIV-1 Integrase Inhibitors:  The 3,3,3‘,3‘-Tetramethyl-1,1‘-spirobi(indan)-5,5‘,6,6‘-tetrol Family
  作者：Valentina Molteni、Denise Rhodes、Kathleen Rubins、Mark Hansen、Frederic D. Bushman、Jay S. Siegel

  DOI：10.1021/jm990600c

  日期：2000.5.1

  Integration is a required step in HIV replication, but as yet no inhibitors of the integration step have been developed for clinical use. Many inhibitors have been identified that are active against purified viral-encoded integrase protein; of these many contain a catechol moiety. Though this substructure contributes potency in inhibitors, it is associated with toxicity and so the utility of catechol-containing inhibitors has been questioned. We have synthesized and tested a systematic series of derivatives of a catechol-containing inhibitor (1) with the goal of identifying catechol isosteres that support inhibition. We find that different patterns of substitution on the aromatic ring suffice for inhibition when Mn2+ is used as a cofactor. Importantly, the efficiency is different when Mg2+, the more likely in vivo cofactor, is used. These data emphasize the importance of assays with Mg2+ and offer new catechol isosteres for use in integrase inhibitors.