氯苯吡醇胺 | 486-16-8

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 氯苯吡醇胺
• 中文别名: 2-[(4-氯苯基)(吡啶-2-基)甲氧基]-N,N-二甲基乙胺；卡比沙明
• 英文名称: 2-[(4-chlorophenyl)-2-pyridinylmethoxy]-N,N-dimethylethanamine
• 英文别名: (+/-)-Carbinoxamine；Carbinoxamine；2-((4-chlorophenyl)(pyridin-2-yl)methoxy)-N,N-dimethylethan-1-amine；2-[(4-chlorophenyl)(pyridin-2-yl)methoxy]-N,N-dimethylethanamine；2-[(4-chlorophenyl)-pyridin-2-ylmethoxy]-N,N-dimethylethanamine
• CAS: 486-16-8
• 化学式: C₁₆H₁₉ClN₂O
• 分子量: 290.793
• InChiKey: OJFSXZCBGQGRNV-UHFFFAOYSA-N

物化性质

• 沸点：
  bp0.1 158-162°
• 物理描述：
  Solid
• 熔点：
  < 25 °C
• 溶解度：
  2.28e-01 g/L
• 保留指数：
  2047;2109;2067;2060;2052;2065;2066.7;2063.3;2070;2075;2080

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

半衰期：10到20小时

Half Life: 10 to 20 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

卡比沙明与自由组胺竞争结合在HA受体位点。这拮抗了组胺对HA受体的作用，导致由组胺HA受体结合引起的负面症状的减少。卡比沙明的抗胆碱能作用似乎是由于中枢抗毒蕈碱效应，这也可能是其镇吐作用的原理，尽管确切机制尚不清楚。

Carbinoxamine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Carbinoxamine's anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

像许多第一代抗组胺药一样，羧苯甲胺并未与肝脏测试异常或临床明显的肝脏损伤有关联。其肝脏安全性的原因可能与每日低剂量和有限的使用持续时间有关。 发生可能性评分：E（不太可能是临床明显肝脏损伤的原因）。 关于羧苯甲胺和其他抗组胺药的安全性及潜在肝毒性的参考资料，在抗组胺药概述部分给出。 药物类别：抗组胺药

Like many first generation antihistamines, carbinoxamine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its hepatic safety may relate to low daily dose and limited duration of use. Likelihood score: E (unlikely to be a cause of clinically apparent liver injury). References on the safety and potential hepatotoxicity of carbinoxamine and other antihistamines are given together in the overview section on antihistamines. Drug Class: Antihistamines

来源:LiverTox

毒理性

• 药物性肝损伤

化合物：卡比沙明

Compound:carbinoxamine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  氯苯吡醇胺 在 双氧水 作用下， 以 甲醇 为溶剂， 反应 168.0h， 生成 carbinoxamine N-oxide
  参考文献：
  名称：

  A chemoselective deoxygenation of N-oxides by sodium borohydride–Raney nickel in water

  摘要：

  A simple and convenient protocol for deoxygenation of aliphatic and aromatic N-oxides to the corresponding amines in good to excellent yield using sodium borohydride-Raney nickel in water is reported. Other functional moieties such as alkenes, halides, ethers, and amides are unaffected under the present reaction condition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.08.045
• 作为产物：
  描述：

  carbinoxamine N-oxide 在 sodium tetrahydroborate 作用下， 以 水 为溶剂， 以96%的产率得到氯苯吡醇胺
  参考文献：
  名称：

  A chemoselective deoxygenation of N-oxides by sodium borohydride–Raney nickel in water

  摘要：

  A simple and convenient protocol for deoxygenation of aliphatic and aromatic N-oxides to the corresponding amines in good to excellent yield using sodium borohydride-Raney nickel in water is reported. Other functional moieties such as alkenes, halides, ethers, and amides are unaffected under the present reaction condition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.08.045

文献信息

• Imidazole and benzimidazole derivatives useful as histamine H3 antagonists
  申请人：Aslanian G. Robert

  公开号：US20060166960A1

  公开（公告）日：2006-07-27

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: n is 2-5; R is R 3 -aryl, R 3 -heteroaryl, R 3 -cycloalkyl, R 3 -heterocycloalkyl, alkyl, haloalkyl, —OR 4 , —SR 4 or —S(O) 1-2 R 5 ; R 1 and R 2 are H or optionally substituted phenyl or optionally substituted and X is —O— or —S—; or R 1 and R 2 , together with the carbon atoms to which they are attached form optionally substituted and X is —O—, —S— or —NR 7 —; Z is and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I; also disclosed are methods of treating allergy, allergy-induced airway responses, congestion, obesity and metabolic syndrome using the compounds of Formula I, as well as combinations with other drugs useful for treating those diseases.

  揭示了以下公式化合物或其药学上可接受的盐或溶剂，其中：n为2-5；R为R3-芳基，R3-杂环芳基，R3-环烷基，R3-杂环烷基，烷基，卤代烷基，—OR4，—SR4或—S(O)1-2R5；R1和R2为H或可选择地取代的苯基或可选择地取代的，X为—O—或—S—；或R1和R2，连同它们连接的碳原子形成可选择地取代的，X为—O—，—S—或—NR7—；Z为，其余变量如规范中所定义；还揭示了包括公式I化合物的药物组合物；还揭示了使用公式I化合物治疗过敏、过敏引起的气道反应、充血、肥胖和代谢综合征的方法，以及与其他用于治疗这些疾病的药物的组合。
• [EN] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES AS HISTAMINE H3 ANTAGONISTS<br/>[FR] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR H3 DE L'HISTAMINE
  申请人：SCHERING CORP

  公开号：WO2003103669A1

  公开（公告）日：2003-12-18

  Disclosed are histamine H3 antagonists of the formula (I) wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula (I) in combination with a H1 receptor antagonist.

  揭示了公式（I）中的组胺H3拮抗剂，其中R1是苯并咪唑酮衍生物，M1和M2是可选择地取代的碳或氮，R2包括可选择地取代的芳基或杂环基，其余变量如规范中所定义。还揭示了包括公式（I）化合物的药物组合物。还揭示了使用公式（I）化合物治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）的方法。还揭示了使用公式（I）化合物与H1受体拮抗剂结合治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）。
• SUBSTITUTED INDOLES
  申请人：Gant Thomas G.

  公开号：US20090191183A1

  公开（公告）日：2009-07-30

  Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了Formula I的替代吲哚半胱氨酸白三烯受体调节剂，其制备方法，药物组合物以及使用方法。
• [EN] TRICYCLIC TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY<br/>[FR] COMPOSÉS TRIAZOLES TRICYCLIQUES MODULANT L'ACTIVITÉ HSP90
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2009139916A1

  公开（公告）日：2009-11-19

  The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

  本发明涉及替代三环三唑化合物和包含替代三环三唑化合物的组合物。该发明还涉及在需要的受体中抑制Hsp90活性的方法，以及预防或治疗高增殖性疾病（如癌症）的方法，其中包括向受体施用本发明的化合物或包含这种化合物的组合物。
• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。

表征谱图