1-(2-phenylethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrazone | 537010-19-8

• 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: 1-(2-phenylethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrazone
• 英文别名: [1-(2-Phenylethyl)benzimidazol-2-yl]hydrazine
• CAS: 537010-19-8
• 化学式: C₁₅H₁₆N₄
• 分子量: 252.319
• InChiKey: TYQYZRNNJHFJGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  55.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α-氧代-2-呋喃乙酸 、 1-(2-phenylethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrazone 以 乙醇 为溶剂， 反应 2.0h， 以65%的产率得到{[1-(2-phenylethyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]hydrazono}(2-furyl)acetic acid
  参考文献：
  名称：

  3-Aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one: A Novel Template for the Design of Highly Selective A_2B Adenosine Receptor Antagonists

  摘要：

  In an effort to identify novel ligands possessing high affinity and selectivity for the A(2B) AR subtype, we further investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones V, previously disclosed by us as selective A(1) AR antagonists. Preliminary assays on a number of triazinobenzimidazoles derived from our "in-house" collection revealed that all the derivatives selected showed significant affinity at A(2B) AR, no affinity at A(3) AR, and various degrees of selectivity toward A(1) and A(2A) ARs. Investigation of a new series featuring modified substituents at the 10-position (4'-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position (X) of the triazinobenzimidazole nucleus, yielded highly potent and selective A(2B) AR antagonists. The presence of a pendant 3-phenyl ring appears to hamper the interaction with A(2A) AR, conferring high A(2B)/A(2A) AR selectivity. Derivative 13 (X = Cl, R = C6H5) is the most potent and selective compound, with an IC50 of 3.10 nM at A(2B) AR and no affinity at A(1), A(2A), and A(3) ARs.

  DOI：

  10.1021/jm201177b
• 作为产物：
  描述：

  2-氯苯并咪唑 在 sodium hydride 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(2-phenylethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrazone
  参考文献：
  名称：

  3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A_2A-Mediated Neuroprotective Effects

  摘要：

  In this study, compound FTBI (3-(2-furyl)-10-(2-phenylethyl)[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one) was selected from a small library of triazinobenzimidazole derivatives as a potent A(2A) adenosine receptor (AR) antagonist and tested for its neuroprotective effects against two different kinds of dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and methamphetamine (METH), in rat PC12 and in human neuroblastoma SH-SYSY cell lines. FTBI, in a concentration range corresponding to its affinity for A(2A) AR subtype, significantly increased the number of viable PC12 cells after their exposure to METH and, to a similar extent, to MPP+, as demonstrated in both trypan blue exclusion assay and in cytological staining. These neuroprotective effects were also observed with a classical A(2A) AR antagonist, ZM241385, and appeared to be completely counteracted by the AR agonist, NECA, supporting A(2A) ARs are directly involved in FTBI-mediated effects. Similarly, in human SH-SYSY cells, FTBI was able to prevent cell toxicity induced by MPP+ and METH, showing that this A(2A) AR antagonist has a neuroprotective effect independently by the specific cell model. Altogether these results demonstrate that the A(2A) AR blockade mediates cell protection against neurotoxicity induced by dopaminergic neurotoxins in dopamine containing cells, supporting the potential we of A(2A) AR antagonists in dopaminergic degenerative diseases including Parkinson's disease.

  DOI：

  10.1021/cn200036s

文献信息

• 3-Aryl-[1,2,4]triazino[4,3-<i>a</i>]benzimidazol-4(10<i>H</i>)-one: A Novel Template for the Design of Highly Selective A_2B Adenosine Receptor Antagonists
  作者：Sabrina Taliani、Isabella Pugliesi、Elisabetta Barresi、Francesca Simorini、Silvia Salerno、Concettina La Motta、Anna Maria Marini、Barbara Cosimelli、Sandro Cosconati、Salvatore Di Maro、Luciana Marinelli、Simona Daniele、Maria Letizia Trincavelli、Giovanni Greco、Ettore Novellino、Claudia Martini、Federico Da Settimo

  DOI：10.1021/jm201177b

  日期：2012.2.23

  In an effort to identify novel ligands possessing high affinity and selectivity for the A(2B) AR subtype, we further investigated the class of 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones V, previously disclosed by us as selective A(1) AR antagonists. Preliminary assays on a number of triazinobenzimidazoles derived from our "in-house" collection revealed that all the derivatives selected showed significant affinity at A(2B) AR, no affinity at A(3) AR, and various degrees of selectivity toward A(1) and A(2A) ARs. Investigation of a new series featuring modified substituents at the 10-position (4'-chlorophenyl or phenylethyl groups), and a chlorine atom at the 7-position (X) of the triazinobenzimidazole nucleus, yielded highly potent and selective A(2B) AR antagonists. The presence of a pendant 3-phenyl ring appears to hamper the interaction with A(2A) AR, conferring high A(2B)/A(2A) AR selectivity. Derivative 13 (X = Cl, R = C6H5) is the most potent and selective compound, with an IC50 of 3.10 nM at A(2B) AR and no affinity at A(1), A(2A), and A(3) ARs.
• 3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-<i>a</i>]benzimidazol-4(10<i>H</i>)-one, a Novel Adenosine Receptor Antagonist with A_2A-Mediated Neuroprotective Effects
  作者：Alessia Scatena、Francesco Fornai、Maria Letizia Trincavelli、Sabrina Taliani、Simona Daniele、Isabella Pugliesi、Sandro Cosconati、Claudia Martini、Federico Da Settimo

  DOI：10.1021/cn200036s

  日期：2011.9.21

  In this study, compound FTBI (3-(2-furyl)-10-(2-phenylethyl)[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one) was selected from a small library of triazinobenzimidazole derivatives as a potent A(2A) adenosine receptor (AR) antagonist and tested for its neuroprotective effects against two different kinds of dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and methamphetamine (METH), in rat PC12 and in human neuroblastoma SH-SYSY cell lines. FTBI, in a concentration range corresponding to its affinity for A(2A) AR subtype, significantly increased the number of viable PC12 cells after their exposure to METH and, to a similar extent, to MPP+, as demonstrated in both trypan blue exclusion assay and in cytological staining. These neuroprotective effects were also observed with a classical A(2A) AR antagonist, ZM241385, and appeared to be completely counteracted by the AR agonist, NECA, supporting A(2A) ARs are directly involved in FTBI-mediated effects. Similarly, in human SH-SYSY cells, FTBI was able to prevent cell toxicity induced by MPP+ and METH, showing that this A(2A) AR antagonist has a neuroprotective effect independently by the specific cell model. Altogether these results demonstrate that the A(2A) AR blockade mediates cell protection against neurotoxicity induced by dopaminergic neurotoxins in dopamine containing cells, supporting the potential we of A(2A) AR antagonists in dopaminergic degenerative diseases including Parkinson's disease.