6-氯苯并咪唑-4-羧酸 | 180569-27-1

• 物质功能分类: 有机原料 - 杂环化合物
• 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: 6-氯苯并咪唑-4-羧酸
• 英文名称: 6-chlorobenzimidazole-4-carboxylic acid
• 英文别名: 6-Chloro-1H-benzo[d]imidazole-4-carboxylic acid；6-chloro-1H-benzimidazole-4-carboxylic acid
• CAS: 180569-27-1
• 化学式: C₈H₅ClN₂O₂
• mdl: MFCD02181085
• 分子量: 196.593
• InChiKey: PLUIBRICHWAFJL-UHFFFAOYSA-N

物化性质

• 沸点：
  552.2±30.0 °C(Predicted)
• 密度：
  1.644±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氯苯并咪唑-4-羧酸 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 N-(exo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-6-chlorobenzimidazole-4-carboxamide
  参考文献：
  名称：

  Benzimidazole Derivatives. 2. Synthesis and Structure−Activity Relationships of New Azabicyclic Benzimidazole-4-carboxylic Acid Derivatives with Affinity for Serotoninergic 5-HT₃ Receptors

  摘要：

  A new series of azabicyclic benzimidazole-4-carboxamides 2-21 and -carboxylates 22-30 were synthesized and evaluated for binding affinity at serotoninergic 5-HT3 and 5-HT4 receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT3 binding site and low to no significant affinity for the 5-HT4 receptor. SAR observations indicated that a halogen atom at the Ii-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT3 affinity and 5-HT3/5-HT4 selectivity, as well as no substitution in this ring. (S)-(-)-N-(Quinuclidin-3-yl)benzimidazo-4-carboxamides 2, 8, and 14 bound at central 5-HT3 sites with high affinity (K-i = 2.6, 0.13, and 1.7 nM, respectively) and excellent selectivity over serotonin 5-HT4 and 5-HT1A receptors (K-i > 1000-10000 dM). Furthermore, these new 5-HT3 receptor ligands were pharmacologically characterized as potent and selective 5-HT3 antagonists in the isolated guinea pig ileum (pA(2) = 9.6, 9.9, and 9.1, respectively).

  DOI：

  10.1021/jm991076c
• 作为产物：
  描述：

  5-氯-7-甲基-1H-苯并咪唑 在 sodium hydroxide 、 potassium permanganate 作用下， 以 水 为溶剂， 反应 5.0h， 以40%的产率得到6-氯苯并咪唑-4-羧酸
  参考文献：
  名称：

  Novel benzimidazole-4-carboxylic acid derivatives as potent and selective 5-HT3 receptor ligands

  摘要：

  A series of benzimidazole-4-carboxylic acid derivatives was synthesized and evaluated for affinity at 5-HT3 and 5-HT4 serotoninergic receptors. Compounds 1b, c and j exhibited high affinity for the 5-HT3 receptors (K-i=6.1, 3.7 and 4.9 nM, respectively) and no significant affinity for 5-HT4 (K-i>1000 nM) and 5-HT1A (K-i>10 000 nM) sites. Preliminary studies showed that 1c displayed activity in the two-compartment behavioural model. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00200-4

文献信息

• Thiazolyl-benzimidazoles
  申请人：Boylan John Frederick

  公开号：US20070203210A1

  公开（公告）日：2007-08-30

  The invention is directed to compounds of formula (1) and pharmaceutically acceptable salts thereof, methods for the preparation thereof, and methods of use thereof.

  这项发明涉及公式（1）的化合物及其药用盐，其制备方法和使用方法。
• Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof
  申请人：MAILLIET Patrick

  公开号：US20080153837A1

  公开（公告）日：2008-06-26

  This invention relates to derivatives of 4-(benzimidazol-2-yl)fluorene and 4-(azabenzimidazol-2-yl)fluorene, to pharmaceutical compositions comprising such derivatives, and to methods of treatment of disorders related to Hsp90 protein activity, comprising administering such derivatives.

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。
• Method for the synthesis of radiolabeled compounds
  申请人：——

  公开号：US20020155063A1

  公开（公告）日：2002-10-24

  The present invention relates to a new method for radiolabeling chemical compounds. The new method attains the goals of simplicity, high radiochemical yields, speed, versatility, and automation. An HPLC injection loop on an HPLC injection valve is loaded with a solution of precursor and the radiolabeling reagent is passed through the loop. The contents of the loop are then quantitatively injected onto the HPLC column for purification. Radiochemical yields are equal to or superior to conventional solution methods in all cases, even though no heat need be applied. Since no vials, transfer lines, cooling, heating, or sealing valves are required, no transfer losses occur, yields are high, and clean-up is minimal. This “loop method” is ideal for the preparation of radiolabeled compounds, in particular those prepared from [ 11 C]-iodomethane.

  本发明涉及一种对化合物进行放射性标记的新方法。新方法实现了简便、高放射化学收率、快速、多功能和自动化的目标。在高效液相色谱注射阀上的高效液相色谱注射环中装入前体溶液，然后将放射性标记试剂通过注射环。然后将回路中的内容物定量注入高效液相色谱柱进行纯化。在所有情况下，尽管无需加热，但放射化学反应的产量与传统溶液法相当或更高。由于不需要小瓶、传输线、冷却、加热或密封阀，因此不会出现传输损失，产量高，清理工作也很少。这种 "循环法 "非常适合制备放射性标记化合物，尤其是由 &lsqb 制备的化合物； 11 C]-碘甲烷制备的化合物。
• Benzimidazole derivatives. Part 1: Synthesis and structure–activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists
  作者：Marı́a L. López-Rodrı́guez、Bellinda Benhamú、Alma Viso、M.José Morcillo、Marta Murcia、Luis Orensanz、M.José Alfaro、M.Isabel Martı́n

  DOI：10.1016/s0968-0896(99)00172-8

  日期：1999.11

  New benzimidazole-4-carboxamides 1-16 and -carboxylates 17-26 were synthesized and evaluated for binding affinity at serotonergic 5-HT4 and 5-HT3 receptors in the CNS. Most of the synthesized compounds exhibited moderate to-very high affinity tin many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor. SAR observations and structural analyses (molecular modeling, INSIGHT II) indicated that the presence of a voluminous substituent in the basic nitrogen atom of the amino moiety and a distance of ca. 8.0 Angstrom from this nitrogen to the aromatic ring are of great importance for high affinity and selectivity for 5-HT4 receptors. These results confirm our recently proposed model for recognition by the 5-HT4 binding site. Amides 12-15 and esters 24 and 25 bound at central 5-HT4 sites with very high affinity (K-j = 0.11-2.9 nM) and excellent selectivity over serotonin 5-HT3, 5-HT2A, and S-HT1A receptors (K-i > 1000-10,000 nM). Analogues 12 (k(i)(5-HT4) = 0.32 nM), 13 (K-i(5-HT4)= 0.11 nM), 14 (K-i(5-HT4) = 0.29 nM) and 15 (K-i(5-HT4) = 0.54 nM) were pharmacologically characterized as selective 5-HT4 antagonists in the isolated guinea pig ileum (pA(2) = 7.6, 7.9, 8.2 and 7.9, respectively), with a potency comparable to the 5-HT4 receptor antagonist RS 39604 (pA(2) = 8.2). The benzimidazoe-4-carboxylic acid derivatives described in this paper represent a novel class of potent and selective 5-HT4 receptor antagonists. In particular, compounds 12-15 could be interesting pharmacological tools for the understanding of the role of 5-HT4 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.
• US6749830B2
  申请人：——

  公开号：US6749830B2

  公开（公告）日：2004-06-15