4-chloro-4'-iodobenzhydryl chloride | 172219-24-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-chloro-4'-iodobenzhydryl chloride
• 英文别名: 1-chloro-4-(chloro(4-iodophenyl)methyl)benzene；1-Chloro-4-[chloro-(4-iodophenyl)methyl]benzene
• CAS: 172219-24-8
• 化学式: C₁₃H₉Cl₂I
• 分子量: 363.025
• InChiKey: JLHGUEBIPLRFRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4-chloro-4'-iodobenzhydryl chloride 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.5h， 生成 2-(2-(4-((4-chlorophenyl)(4-iodophenyl)methyl)piperazin-1-yl)ethoxy)acetic acid
  参考文献：
  名称：

  Route to Prolonged Residence Time at the Histamine H₁ Receptor: Growing from Desloratadine to Rupatadine

  摘要：

  Drug-target binding kinetics are an important predictor of in vivo drug efficacy, yet the relationship between ligand structures and their binding kinetics is often poorly understood. We show that both rupatadine (1) and desloratadine (2) have a long residence time at the histamine H-1 receptor (H1R). Through development of a [H-3]levocetirizine radiolabel, we find that the residence time of 1 exceeds that of 2 more than 10-fold. This was further explored with 22 synthesized rupatadine and desloratadine analogues. Methylene-linked cycloaliphatic or beta-branched substitutions of desloratadine increase the residence time at the H1R, conveying a longer duration of receptor antagonism. However, cycloaliphatic substituents directly attached to the piperidine amine (i.e., lacking the spacer) have decreased binding affinity and residence time compared to their methylene-linked structural analogues. Guided by docking studies, steric constraints within the binding pocket are hypothesized to explain the observed differences in affinity and binding kinetics between analogues.

  DOI：

  10.1021/acs.jmedchem.9b00447
• 作为产物：
  描述：

  4-氯苯基溴化镁 在 氯化亚砜 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 4-chloro-4'-iodobenzhydryl chloride
  参考文献：
  名称：

  Route to Prolonged Residence Time at the Histamine H₁ Receptor: Growing from Desloratadine to Rupatadine

  摘要：

  Drug-target binding kinetics are an important predictor of in vivo drug efficacy, yet the relationship between ligand structures and their binding kinetics is often poorly understood. We show that both rupatadine (1) and desloratadine (2) have a long residence time at the histamine H-1 receptor (H1R). Through development of a [H-3]levocetirizine radiolabel, we find that the residence time of 1 exceeds that of 2 more than 10-fold. This was further explored with 22 synthesized rupatadine and desloratadine analogues. Methylene-linked cycloaliphatic or beta-branched substitutions of desloratadine increase the residence time at the H1R, conveying a longer duration of receptor antagonism. However, cycloaliphatic substituents directly attached to the piperidine amine (i.e., lacking the spacer) have decreased binding affinity and residence time compared to their methylene-linked structural analogues. Guided by docking studies, steric constraints within the binding pocket are hypothesized to explain the observed differences in affinity and binding kinetics between analogues.

  DOI：

  10.1021/acs.jmedchem.9b00447

文献信息

• Synthesis of [2-{(4-chlorophenyl) (4-[125I]iodophenyl)} methoxyethyl]-1-piperidine-3-carboxylic acid, [125I]CIPCA: A potential radiotracer for GABA uptake sites
  作者：Marcian E. Van Dort、David L. Gildersleeve、Donald M. Wieland

  DOI：10.1002/jlcr.2580361008

  日期：1995.10

  The synthesis of racemic [2-(4-Chlorophenyl) (4-iodophenyl)} methoxyethyl]-1-piperidine-3-carboxylic acid, (CIPCA) and its radioiodinated analog [125ßI]CIPCA is described. CIPCA was synthesized from 4-iodobenzoyl chloride in five steps in 16% overall yield. Ammonium sulfate catalyzed solid-state isotopic exchange of CIPCA with Na125I provided [125I]CIPCA in 34% isolated radiochemical yield at a specific activity of 118 Ci/mmol. [125ICIPCA] demonstrated moderate brain extraction and good in vivo radiostability in preliminary biodistribution studies conducted in CD-1 mice. [125I]CIPCA is a potentially useful radiotracer for study of the GABA uptake system.

  报道了外消旋[2-(4-氯苯基)(4-碘苯基)}甲氧乙基]-1-哌啶-3-羧酸(CIPCA)及其放射性碘标记类似物[125I]CIPCA的合成。CIPCA由4-碘苯甲酰氯经五步合成,总收率为16%。硫酸铵催化的CIPCA与Na125I的固态同位素交换法提供了比活度为118 Ci/mmol的[125I]CIPCA,其分离放化收率为34%。在CD-1小鼠中进行的初步生物分布研究显示,[125I]CIPCA显示出适度的脑摄取和良好的体内放射稳定性。[125I]CIPCA是一种可能有用的GABA摄取系统研究放射性示踪剂。