5-({3-methyl-5-[(phenylsulfonyl)methyl]phenoxy}methyl)-1H-benzo[d]imidazol-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-({3-methyl-5-[(phenylsulfonyl)methyl]phenoxy}methyl)-1H-benzo[d]imidazol-2-amine
• 英文别名: 6-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]-1H-benzimidazol-2-amine
• 化学式: C₂₂H₂₁N₃O₃S
• 分子量: 407.493
• InChiKey: BIOWNCLYQIVDGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-二氨基苯甲酸甲酯 在 偶氮二甲酸二叔丁酯 、 二异丁基氢化铝 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 22.0h， 生成 5-({3-methyl-5-[(phenylsulfonyl)methyl]phenoxy}methyl)-1H-benzo[d]imidazol-2-amine
  参考文献：
  名称：

  Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits

  摘要：

  Sphingosine kinase (SphK) is the major source of the lipid mediator and G protein-coupled receptor agonist sphingosine-l-phosphate (S1P). SIP promotes cell growth, survival, and migration and is a key regulator of lymphocyte trafficking. Inhibition of SIP signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme-based high-throughput screen yielded two attractive chemotypes capable of inhibiting SO formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with 2 orders of magnitude improved potency. Compound 22a inhibited SphK1 with an IC50 of 2 nM and was more than 100-fold selective for SphK1 over the SphK2 isoform. Through the modification of tail-region substituents, the specificity of inhibition for SphK1 and SphK2 could be modulated, yielding SphK1-selective, potent SphK1/2 dual, or SphK2-preferential inhibitors.

  DOI：

  10.1021/acs.jmedchem.7b00070

文献信息

• Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits
  作者：Mark E. Schnute、Matthew D. McReynolds、Jeffrey Carroll、Jill Chrencik、Maureen K. Highkin、Kaliapan Iyanar、Gina Jerome、John W. Rains、Matthew Saabye、Jeffrey A. Scholten、Matthew Yates、Marek M. Nagiec

  DOI：10.1021/acs.jmedchem.7b00070

  日期：2017.3.23

  Sphingosine kinase (SphK) is the major source of the lipid mediator and G protein-coupled receptor agonist sphingosine-l-phosphate (S1P). SIP promotes cell growth, survival, and migration and is a key regulator of lymphocyte trafficking. Inhibition of SIP signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme-based high-throughput screen yielded two attractive chemotypes capable of inhibiting SO formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with 2 orders of magnitude improved potency. Compound 22a inhibited SphK1 with an IC50 of 2 nM and was more than 100-fold selective for SphK1 over the SphK2 isoform. Through the modification of tail-region substituents, the specificity of inhibition for SphK1 and SphK2 could be modulated, yielding SphK1-selective, potent SphK1/2 dual, or SphK2-preferential inhibitors.