4,5-Dimethoxy-1-phenylbenzimidazole | 238426-47-6

• 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: 4,5-Dimethoxy-1-phenylbenzimidazole
• 英文别名: 5-Substituted 1-Phenylbenzimidazole 30
• CAS: 238426-47-6
• 化学式: C₁₅H₁₄N₂O₂
• 分子量: 254.288
• InChiKey: JRWVZOGXZFWDAG-UHFFFAOYSA-N

物化性质

• 沸点：
  420.0±48.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-Dimethoxy-1-phenylbenzimidazole 在 lithium methanethiolate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以88%的产率得到4,5-Dihydroxy-1-phenylbenzimidazole
  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
• 作为产物：
  描述：

  3,4-dimethoxy-2-nitrobenzoic acid chloride 在 palladium on activated charcoal copper(l) iodide 、 sodium azide 、 氢气 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙二醇甲醚 、 乙酸乙酯 、 丙酮 为溶剂， 5.0 ℃ 、413.68 kPa 条件下， 反应 18.17h， 生成 4,5-Dimethoxy-1-phenylbenzimidazole
  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
• US6218388B1
  申请人：——

  公开号：US6218388B1

  公开（公告）日：2001-04-17
• [EN] HYDROXAMIC ACID MACROCYCLIC DERIVATIVES, PREPARATION METHOD AND COMPOSITIONS CONTAINING SAME<br/>[FR] DERIVES MACROCYCLIQUES DE L'ACIDE HYDROXAMIQUE, LEUR PREPARATION ET LES COMPOSITIONS QUI LES CONTIENNENT
  申请人：AVENTIS PHARMA SA

  公开号：WO2001040198A2

  公开（公告）日：2001-06-07

  Dérivés macrocycliques de l'acide hydroxamique de formule générale (I) dans laquelle Y est -CH2-, -CH2-CH2- ou -CH=CH- et Z et Z' représentent -CH2- ou bien Y-Z ou Y-Z' représentent -CH=CH- et Z' ou Z sont définis comme ci-avant; X est -CH2-, O ou S; R1 est phényle non substitué ou substitué ou cycloalcoyle (5 ou 6 chaînons), hétérocyclyle mono ou bicyclique (5 à 10 chaînons), saturé ou insaturé (1 à 3 hétéroatomes: N, O ou S), éventuellement substitué ou N-oxydé, ou alcoyle éventuellement substitué; R2 est H, alcoyle ou hydroxyalcoyle éventuellement substitués; R3 est H, alcoyle, alcoyloxycarbonyle, carbamoyle, alcoylcarbamoyle ou dialcoylcarbamoyle, ou bien R2 et R3 forment avec les atomes auquels ils sont attachés, un hétérocycle azoté à 5 ou 6 chaînons pouvant en outre contenir un autre hétéroatome choisi parmi N, O ou S, et éventuellement substitué, par un radical alcoyle, hydroxyalcoyle ou OH; R4 et R'4 sont identiques ou différents et représentent H, OH, alcoyle, hydroxyalcoyle ou alcoyloxy; les radicaux alcoyle ou acyle (1 à 4C) sont droits ou ramifiés, ainsi que leurs sels lorsqu'ils existent et lorsque R4 et R'4 sont différents, leurs formes diastéréoisomères ou leurs mélanges. Les dérivés de formule générale (I) sont particulièrement intéressants comme antimicrobiens.
• 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.