3-(((5-bromo-2-nitrophenyl)amino)methyl)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(((5-bromo-2-nitrophenyl)amino)methyl)benzonitrile
• 英文别名: 3-[(5-Bromo-2-nitroanilino)methyl]benzonitrile
• 化学式: C₁₄H₁₀BrN₃O₂
• 分子量: 332.156
• InChiKey: URMDLDFJGQECNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(((5-bromo-2-nitrophenyl)amino)methyl)benzonitrile 在 lithium aluminium tetrahydride 、 铁粉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 4-bromo-N-(3-((6-bromo-1H-benzo[d]imidazol-1-yl)methyl)-benzyl)-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to in Vivo Pharmacodynamic Activity

  摘要：

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.

  DOI：

  10.1021/acs.jmedchem.9b01809
• 作为产物：
  描述：

  3-氰基苄胺 、 2,4-二溴硝基苯 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以13%的产率得到3-(((5-bromo-2-nitrophenyl)amino)methyl)benzonitrile
  参考文献：
  名称：

  Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to in Vivo Pharmacodynamic Activity

  摘要：

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.

  DOI：

  10.1021/acs.jmedchem.9b01809

文献信息

• Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to <i>in Vivo</i> Pharmacodynamic Activity
  作者：Marta Serafini、Enza Torre、Silvio Aprile、Erika Del Grosso、Alessandro Gesù、Alessia Griglio、Giorgia Colombo、Cristina Travelli、Salvatore Paiella、Annalisa Adamo、Elena Orecchini、Alice Coletti、Maria Teresa Pallotta、Stefano Ugel、Alberto Massarotti、Tracey Pirali、Silvia Fallarini

  DOI：10.1021/acs.jmedchem.9b01809

  日期：2020.3.26

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.