1-苯基苯并咪唑-5-硫醇 | 238426-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 1-苯基苯并咪唑-5-硫醇
• 英文名称: 1-Phenyl-1H-benzimidazole-5-thiol
• 英文别名: 1-phenylbenzimidazole-5-thiol
• CAS: 238426-41-0
• 化学式: C₁₃H₁₀N₂S
• 分子量: 226.302
• InChiKey: QJMFHEHQAWFOPG-UHFFFAOYSA-N

物化性质

• 沸点：
  421.8±37.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  18.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  S-(1-phenylbenzimidazolyl)dimethylthiocarbamate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以56%的产率得到1-苯基苯并咪唑-5-硫醇
  参考文献：
  名称：

  Structure−Activity Relationships for 5-Substituted 1-Phenylbenzimidazoles as Selective Inhibitors of the Platelet-Derived Growth Factor Receptor

  摘要：

  Following an earlier discovery of 1-phenylbenzimidazoles as ATP-site inhibitors of the platelet-derived growth factor receptor (PDGFR), further structure-activity relationships for analogues (particularly 5-substituted derivatives) are reported. The data are consistent with a binding model (constructed from the homology-modeled structure of the catalytic subunit of the PDGFR using protein kinase A as the template) in which the ligand binds in the relatively narrow ATP site, with the phenyl ring pointing toward the interior of the pocket and the 5-position of the benzimidazole ring toward the mouth of the pocket. The narrow binding pocket allows a maximum torsion angle between the phenyl and benzimidazole rings of about 40 degrees, consistent with that calculated (43.6 degrees) for the minimum-energy conformation of the unsubstituted free ligand. The inactivity of 7- or 2'-substituted analogues is consistent with the greater torsion angle (and thus larger ligand cross-section) of such substituted analogues. There is substantial bulk tolerance for 5-substituents, which protrude out of the mouth of the hydrophobic pocket, with the most effective analogues being those bearing weak bases. On the basis of this model, 5-OR derivatives bearing cationic side chains were prepared as soluble analogues, and these showed sub-micromolar potencies against the isolated PDGFR enzyme. They were also moderately effective inhibitors of autophosphorylation of PDGFR in rat aortic vascular smooth muscle cells, with IC(50)s in the range 0.1-1 mu 1M.

  DOI：

  10.1021/jm980658b

文献信息

• US5990146A
  申请人：——

  公开号：US5990146A

  公开（公告）日：1999-11-23
• US6191146B1
  申请人：——

  公开号：US6191146B1

  公开（公告）日：2001-02-20
• US6218388B1
  申请人：——

  公开号：US6218388B1

  公开（公告）日：2001-04-17
• Structure−Activity Relationships for 5-Substituted 1-Phenylbenzimidazoles as Selective Inhibitors of the Platelet-Derived Growth Factor Receptor
  作者：Brian D. Palmer、Alan J. Kraker、Brian G. Hartl、Athanasia D. Panopoulos、Robert L. Panek、Brian L. Batley、Gina H. Lu、Susanne Trumpp-Kallmeyer、H. D. Hollis Showalter、William A. Denny

  DOI：10.1021/jm980658b

  日期：1999.7.1

  Following an earlier discovery of 1-phenylbenzimidazoles as ATP-site inhibitors of the platelet-derived growth factor receptor (PDGFR), further structure-activity relationships for analogues (particularly 5-substituted derivatives) are reported. The data are consistent with a binding model (constructed from the homology-modeled structure of the catalytic subunit of the PDGFR using protein kinase A as the template) in which the ligand binds in the relatively narrow ATP site, with the phenyl ring pointing toward the interior of the pocket and the 5-position of the benzimidazole ring toward the mouth of the pocket. The narrow binding pocket allows a maximum torsion angle between the phenyl and benzimidazole rings of about 40 degrees, consistent with that calculated (43.6 degrees) for the minimum-energy conformation of the unsubstituted free ligand. The inactivity of 7- or 2'-substituted analogues is consistent with the greater torsion angle (and thus larger ligand cross-section) of such substituted analogues. There is substantial bulk tolerance for 5-substituents, which protrude out of the mouth of the hydrophobic pocket, with the most effective analogues being those bearing weak bases. On the basis of this model, 5-OR derivatives bearing cationic side chains were prepared as soluble analogues, and these showed sub-micromolar potencies against the isolated PDGFR enzyme. They were also moderately effective inhibitors of autophosphorylation of PDGFR in rat aortic vascular smooth muscle cells, with IC(50)s in the range 0.1-1 mu 1M.