methyl 2-[(tert-butoxycarbonyl)amino]-1H-benzo[d]imidazole-5-carboxylate | 1420352-40-4

• 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: methyl 2-[(tert-butoxycarbonyl)amino]-1H-benzo[d]imidazole-5-carboxylate
• 英文别名: 2-tert-butoxycarbonylamino-1H-benzimidazole-5-carboxylic acid methyl ester；methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3H-benzimidazole-5-carboxylate
• CAS: 1420352-40-4
• 化学式: C₁₄H₁₇N₃O₄
• 分子量: 291.307
• InChiKey: ADZNDQPLECAZBV-UHFFFAOYSA-N

物化性质

• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-[(tert-butoxycarbonyl)amino]-1H-benzo[d]imidazole-5-carboxylate 在 偶氮二甲酸二叔丁酯 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 18.0h， 生成 tert-butyl [5-({3-methyl-5-[(phenylsulfonyl)methyl]phenoxy}methyl)-1H-benzo[d]imidazol-2-yl]carbamate
  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
• 作为产物：
  描述：

  3,4-二氨基苯甲酸甲酯 、 N,N'-bis-Boc-S-methyl-isothiourea 在 camphor-10-sulfonic acid 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 methyl 2-[(tert-butoxycarbonyl)amino]-1H-benzo[d]imidazole-5-carboxylate
  参考文献：
  名称：

  Neutrophil inhibitors to reduce inflammatory response

  摘要：

  该发明提供了从以下组合中选择的新化合物：1本发明的化合物对治疗和预防与不良或异常炎症反应相关的各种疾病和病况，如缺血再灌注损伤，具有益处。因此，该发明还提供了包括这些化合物的药物组合物。该发明还提供了使用这些化合物或含有它们的组合物进行上述疾病的治疗或预防的方法。

  公开号：

  US20040006104A1

文献信息

• Neutrophil inhibitors to reduce inflammatory response
  申请人：The Procter & Gamble Company

  公开号：US20040006104A1

  公开（公告）日：2004-01-08

  The invention provides novel compounds selected from the group consisting of: 1 The compounds of the present invention are useful for the treatment and prevention of a variety of diseases and conditions associated with undesirable or abnormal inflammatory responses, such as ischemia-reperfusion injury. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment or prevention for the above disorders using theses compounds or the compositions containing them.

  该发明提供了从以下组合中选择的新化合物：1本发明的化合物对治疗和预防与不良或异常炎症反应相关的各种疾病和病况，如缺血再灌注损伤，具有益处。因此，该发明还提供了包括这些化合物的药物组合物。该发明还提供了使用这些化合物或含有它们的组合物进行上述疾病的治疗或预防的方法。
• 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.