卡拉美芬 | 77-22-5

• 物质功能分类: 原料药 - 呼吸系统用药 - 镇咳药
• 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: 卡拉美芬
• 中文别名: 卡拉米芬
• 英文名称: caramiphen
• 英文别名: 1-phenyl-cyclopentanecarboxylic acid-(2-diethylamino-ethyl ester)；1-Phenyl-cyclopentancarbonsaeure-(2-diaethylamino-aethylester)；1-phenylcyclopentanecarboxylic acid 2-(diethylamino)ethyl ester；1-Phenyl-cyclopentan-carbonsaeure-(1)-<2-diethylamino-ethylester>；1-Phenyl-cyclopentan-1-carbonsaeure-<2-diethylamino-ethylester>；2-(diethylamino)ethyl 1-phenylcyclopentane-1-carboxylate
• CAS: 77-22-5
• 化学式: C₁₈H₂₇NO₂
• mdl: MFCD00063432
• 分子量: 289.418
• InChiKey: OFAIGZWCDGNZGT-UHFFFAOYSA-N

物化性质

• 沸点：
  bp0.07 112-115°
• 保留指数：
  1980.5;2005;1971

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

制备方法与用途

概述

卡拉美芬能抑制咳嗽中枢，是一种非成瘾性的镇咳药，还具有局部麻醉和轻度支气管扩张作用，但不具备镇痛或呼吸抑制效果。

化学性质

卡拉美芬为液体。沸点在156-158℃（0.93kPa）或110-115℃（6.65×10^-3kPa）。

用途

与乙烷二磺酸生成盐，即咳美芬，具有抑制咳嗽中枢的作用。适用于治疗肺结核、气管炎、支气管炎及流感引起的咳嗽。

生产方法

由1-苯基环戊烷甲酰氯与二乙氨基乙醇酯化而得。具体步骤如下：将1-苯基环戊烷甲酰氯加入干燥反应锅内，搅拌冷却至10-15℃，滴加二乙氨基乙醇，内温逐渐上升至110℃并在2.5-3小时内加完，继续搅拌30分钟，升温至115-125℃反应2-2.5小时。趁热放料，过夜放置。加入5倍量的水溶解，用10%盐酸调节pH值至6-7。过滤除去不溶物。滤液以苯提取后，加活性炭于70-80℃脱色2小时，再次过滤。滤液中加入碳酸钠调至中性，析出油层，使用硫酸钠饱和溶液洗涤至中性，再加无水硫酸钠干燥，过滤，得到咳美芬盐基。

反应信息

• 作为反应物：
  描述：

  卡拉美芬 在 copper(II) nitrate trihydrate 、 (6,6’-dimethoxy-[1,1 ‘-biphenyl]-2,2’-diyl)bis(bis(3 ,5-dimethyl-phenyl)phosphine) 、 [(1,5-cyclooctadiene)(OH)iridium(I)]2 、 cesium fluoride 作用下， 以 甲醇 、 正己烷 、 水 为溶剂， 反应 126.0h， 生成 2-(diethylamino)ethyl 1-(p-cyanophenyl)cyclopentanecarboxylate
  参考文献：
  名称：

  para-C–H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst

  摘要：

  A highly para-selective aromatic C-H borylation has been accomplished. By a new iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C-H borylation of monosubstituted benzenes can be affected with para-selectivity up to 91%. This catalytic system is quite different from the usual iridium catalysts that cannot distinguish meta- and para-C-H bonds of monosubstituted benzene derivatives, resulting in the preferred formation of meta-products. The para-selectivity increases with increasing bulkiness of the substituent on the arene, indicating that the regioselectivity of the present reaction is primarily controlled by steric repulsion between substrate and catalyst. Caramiphen, an anticholinergic drug used in the treatment of Parkinsons disease, was converted into five derivatives via our para-selective borylation. The present [Ir(cod)OH](2)/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, para-selective, aromatic C-H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.

  DOI：

  10.1021/jacs.5b02052
• 作为产物：
  描述：

  1-苯基环戊烷羧酸 在 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 卡拉美芬
  参考文献：
  名称：

  para-C–H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst

  摘要：

  A highly para-selective aromatic C-H borylation has been accomplished. By a new iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C-H borylation of monosubstituted benzenes can be affected with para-selectivity up to 91%. This catalytic system is quite different from the usual iridium catalysts that cannot distinguish meta- and para-C-H bonds of monosubstituted benzene derivatives, resulting in the preferred formation of meta-products. The para-selectivity increases with increasing bulkiness of the substituent on the arene, indicating that the regioselectivity of the present reaction is primarily controlled by steric repulsion between substrate and catalyst. Caramiphen, an anticholinergic drug used in the treatment of Parkinsons disease, was converted into five derivatives via our para-selective borylation. The present [Ir(cod)OH](2)/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, para-selective, aromatic C-H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.

  DOI：

  10.1021/jacs.5b02052

文献信息

• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。
• Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors
  申请人：Goble D. Stephen

  公开号：US20070238723A1

  公开（公告）日：2007-10-11

  Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula I: which are used to modulate the CCR-2 chemokine receptor to prevent or treat inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis; and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions.

  环戊基化合物通过酰胺基团与苯并噁唑基团相连，利用苯并噁唑环的环氮原子，并进一步用杂环基团取代，这些化合物由式I表示： 用于调节CCR-2趋化因子受体，以预防或治疗炎症和免疫调节性疾病和疾病，过敏性疾病，包括过敏性鼻炎，皮炎，结膜炎和哮喘，以及类风湿性关节炎和动脉粥样硬化等自身免疫病理病变；以及包含这些化合物的药物组合物和这些化合物和组合物的使用。
• [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。
• 3-Aminocyclopentanecarboxamides as Modulators of Chemokine Receptors
  申请人：Xue Chu-Biao

  公开号：US20070149532A1

  公开（公告）日：2007-06-28

  The present invention is directed to compounds of Formula I: I which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及化合物I的化合物：I，这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。

表征谱图