1-Phenylbenzimidazole deriv. 58 | 667919-14-4

• 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: 1-Phenylbenzimidazole deriv. 58
• 英文别名: 1-phenylbenzimidazole-4-carboxylic acid
• CAS: 667919-14-4
• 化学式: C₁₄H₁₀N₂O₂
• mdl: MFCD23674690
• 分子量: 238.246
• InChiKey: NHFKGMARTXZVJH-UHFFFAOYSA-N

物化性质

• 沸点：
  492.5±37.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甘氨酸乙酯盐酸盐 、 1-Phenylbenzimidazole deriv. 58 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以44%的产率得到
  参考文献：
  名称：

  Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1α prolyl hydroxylase-2 inhibitors

  摘要：

  We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.012
• 作为产物：
  描述：

  3-甲基-2-硝基苯胺 在 palladium on activated charcoal potassium permanganate 、 copper(l) iodide 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙二醇甲醚 、 叔丁醇 为溶剂， 反应 19.0h， 生成 1-Phenylbenzimidazole deriv. 58
  参考文献：
  名称：

  Structure−Activity Relationships for 1-Phenylbenzimidazoles as Selective ATP Site Inhibitors of the Platelet-Derived Growth Factor Receptor

  摘要：

  1-Phenylbenzimidazoles are shown to be a new class of ATP-site inhibitors of the platelet-derived growth factor receptor (PDGFR). Structure-activity relationships (SARs) are narrow, with closely related heterocycles being inactive. A systematic study of substituted 1-phenyl-benzimidazoles showed clear SARs. Substituents at the 4'- and 3'-positions of the phenyl ring are tolerated but do not significantly improve activity, while substituents at the 2'-position abolish it. Substituents in the 2-, 4-, and 7-positions of the benzimidazole ring (with the exception of 4-OH) also abolish activity. Most substituents at the 5- and B-positions maintain or increase activity, with the 5-OH, 5-OMe, 5-COMe, and 5-CO2Me analogues being >10-fold more potent than the parent 1-phenylbenzimidazole. The 5-OMe analogue was both the most potent inhibitor, and showed the highest selectivity (50-fold) between PDGFR and FGFR isolated enzymes, and also a moderately effective inhibitor (IC50 = 1.9 mu M) of PDGF-stimulated PDGFR autophosphorylation in rat aorta smooth muscle cells.

  DOI：

  10.1021/jm9804681

文献信息

• Structure−Activity Relationships for 1-Phenylbenzimidazoles as Selective ATP Site Inhibitors of the Platelet-Derived Growth Factor Receptor
  作者：Brian D. Palmer、Jeff B. Smaill、Maruta Boyd、Diane H. Boschelli、Annette M. Doherty、James M. Hamby、Sonya S. Khatana、James B. Kramer、Alan J. Kraker、Robert L. Panek、Gina H. Lu、Tawny K. Dahring、R. Thomas Winters、H. D. Hollis Showalter、William A. Denny

  DOI：10.1021/jm9804681

  日期：1998.12.1

  1-Phenylbenzimidazoles are shown to be a new class of ATP-site inhibitors of the platelet-derived growth factor receptor (PDGFR). Structure-activity relationships (SARs) are narrow, with closely related heterocycles being inactive. A systematic study of substituted 1-phenyl-benzimidazoles showed clear SARs. Substituents at the 4'- and 3'-positions of the phenyl ring are tolerated but do not significantly improve activity, while substituents at the 2'-position abolish it. Substituents in the 2-, 4-, and 7-positions of the benzimidazole ring (with the exception of 4-OH) also abolish activity. Most substituents at the 5- and B-positions maintain or increase activity, with the 5-OH, 5-OMe, 5-COMe, and 5-CO2Me analogues being >10-fold more potent than the parent 1-phenylbenzimidazole. The 5-OMe analogue was both the most potent inhibitor, and showed the highest selectivity (50-fold) between PDGFR and FGFR isolated enzymes, and also a moderately effective inhibitor (IC50 = 1.9 mu M) of PDGF-stimulated PDGFR autophosphorylation in rat aorta smooth muscle cells.
• Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1α prolyl hydroxylase-2 inhibitors
  作者：Mike Frohn、Vellarkad Viswanadhan、Alexander J. Pickrell、Jennifer E. Golden、Kristine M. Muller、Roland W. Bürli、Gloria Biddlecome、Sean C. Yoder、Norma Rogers、Jennifer H. Dao、Randall Hungate、Jennifer R. Allen

  DOI：10.1016/j.bmcl.2008.08.012

  日期：2008.9

  We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro. (C) 2008 Elsevier Ltd. All rights reserved.