1-(4-bromobenzyl)-2-ethyl-1H-benzimidazole | 575465-30-4

• 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-(4-bromobenzyl)-2-ethyl-1H-benzimidazole
• 英文别名: 1-[(4-Bromophenyl)methyl]-2-ethylbenzimidazole
• CAS: 575465-30-4
• 化学式: C₁₆H₁₅BrN₂
• mdl: MFCD13851138
• 分子量: 315.212
• InChiKey: UCVZUFVLXAJJGP-UHFFFAOYSA-N

物化性质

• 沸点：
  475.3±28.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-bromobenzyl)-2-ethyl-1H-benzimidazole 在 sodium hydroxide 、 四(三苯基膦)钯 、 苯甲醚 、 三氟乙酸 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 3.0h， 生成 3-[4-[(2-Ethylbenzimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophene-2-sulfonamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of the First Selective Nonpeptide AT₂ Receptor Agonist

  摘要：

  The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K-i value of 0.4 nM for the AT(2) receptor and a K-i > 10 muM for the AT, receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT2 receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT2 receptor in more detail.

  DOI：

  10.1021/jm049715t
• 作为产物：
  描述：

  邻苯二胺 在 盐酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.25h， 生成 1-(4-bromobenzyl)-2-ethyl-1H-benzimidazole
  参考文献：
  名称：

  双重血管紧张素II /内皮素A受体拮抗剂4'-[[（苯并咪唑-1-基）甲基]联苯-2-磺酰胺衍生物的合成及生物学评价

  摘要：

  合成了一系列4'-[[（苯并咪唑-1-基）甲基]联苯-2-磺酰胺衍生物（Ia-11），并对其进行了生物学评估。发现最活跃的化合物Ig拮抗Ang II AT 1和内皮素ET A受体（AT 1 IC 50  = 8.5，ET A IC 50  = 8.9 nM），并且在RHRs中比氯沙坦更有效，没有显着性对心率的影响。初步的结构-活性关系也在本文中进行了讨论。

  DOI：

  10.1016/j.bmc.2012.06.011

文献信息

• 2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands
  作者：Tamal Roy、Nadia N. Petersen、Greeshma Gopalan、Johan Gising、Mathias Hallberg、Mats Larhed

  DOI：10.1016/j.bmc.2022.116804

  日期：2022.7

  comprising a benzimidazole rather than the imidazole ring that is common in AT2R ligands e.g. in the AT2R agonist C21, can provide both high affinity and receptor selectivity. In particular, compounds encompassing benzimidazoles, substituted in the 2-position with small bulky groups such as an isopropyl (Ki = 4.0 nM) or a tert-butyl (Ki = 5.3 nM) or alternatively a thiazole heterocycle (Ki = 5.1 nM)

  包含苯并咪唑而不是在AT 2 R 配体例如AT 2 R 激动剂C21 中常见的咪唑环的配体可以提供高亲和力和受体选择性。特别地，包括苯并咪唑的化合物，在 2 位被小体积基团取代，例如异丙基 ( K i  = 4.0 nM) 或叔丁基 ( K i  = 5.3 nM) 或噻唑杂环 ( K i  = 5.1 nM) 表现出高亲和力和 AT 2 R 选择性。AT 1中的正丁基链R 选择性沙坦，使配体的受体选择性降低。迄今为止报道的大多数 AT 2 R 选择性配体中存在的联芳基支架上的异丁基最初来源于非选择性强效 AT 1 R/AT 2 R 配体 L-162,313。值得注意的是，在本文讨论的所有配体中，异丁基被正丙基取代，并且提供了对AT 2 R具有高亲和力的配体，此外它们中的大多数表现出良好的AT 2 R/AT 1 R选择性。在不同位置引入氟原子对亲和力数据没有明显影响。带有噻唑或叔叔的配体连接到
• [EN] TRICYCLIC COMPOUNDS USEFUL AS ANGIOTENSIN II AGONISTS<br/>[FR] COMPOSES TRICYCLIQUES UTILISES COMME AGONISTES DE L'ANGIOTENSINE II
  申请人：VICORE PHARMA AB

  公开号：WO2003064414A1

  公开（公告）日：2003-08-07

  There is provided compounds of formula (I), wherein R1, X1, X2, X3, X4, Y1, Y2, Y3, Y4, Z1, Z2, R2 and R3 have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful as selective agonists of the AT2 receptor, and thus, in particular, in the treatment of inter alia gastrointestinal conditions, such as dyspepsia, IBS and MOF, and cardiovascular disorders.
• Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists
  作者：Renren Bai、Zhen Wei、Jie Liu、Weijia Xie、Hequan Yao、Xiaoming Wu、Jieyun Jiang、Qiujuan Wang、Jinyi Xu

  DOI：10.1016/j.bmc.2012.06.011

  日期：2012.8

  A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia–Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure–activity relationships

  合成了一系列4'-[[（苯并咪唑-1-基）甲基]联苯-2-磺酰胺衍生物（Ia-11），并对其进行了生物学评估。发现最活跃的化合物Ig拮抗Ang II AT 1和内皮素ET A受体（AT 1 IC 50  = 8.5，ET A IC 50  = 8.9 nM），并且在RHRs中比氯沙坦更有效，没有显着性对心率的影响。初步的结构-活性关系也在本文中进行了讨论。
• Design, Synthesis, and Biological Evaluation of the First Selective Nonpeptide AT₂ Receptor Agonist
  作者：Yiqian Wan、Charlotta Wallinder、Bianca Plouffe、Hélène Beaudry、A. K. Mahalingam、Xiongyu Wu、Berndt Johansson、Mathias Holm、Milad Botoros、Anders Karlén、Anders Pettersson、Fred Nyberg、Lars Fändriks、Nicole Gallo-Payet、Anders Hallberg、Mathias Alterman

  DOI：10.1021/jm049715t

  日期：2004.11.1

  The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K-i value of 0.4 nM for the AT(2) receptor and a K-i > 10 muM for the AT, receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT2 receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT2 receptor in more detail.