2-[2-[1-(4-氯苯基)-1-苯基-乙氧基]乙基]-1-甲基吡咯烷 | 7723-51-5

• 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: 2-[2-[1-(4-氯苯基)-1-苯基-乙氧基]乙基]-1-甲基吡咯烷
• 中文别名: 聚[氧代[(羟甲基)-1,2-乙二基]],a-(9Z)-9-十八碳烯基-w-羟基-(9CI)
• 英文名称: Clemastine
• 英文别名: Clemastin；2-[2-[1-(4-Chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine
• CAS: 7723-51-5；15686-51-8；61826-27-5；61826-28-6；61826-31-1；63813-90-1；63813-91-2
• 化学式: C₂₁H₂₆ClNO
• 分子量: 343.897
• InChiKey: YNNUSGIPVFPVBX-UHFFFAOYSA-N

物化性质

• 比旋光度：
  D20 +33.6° (ethanol)
• 沸点：
  bp0.02 154°
• 密度：
  1.097±0.06 g/cm3(Predicted)
• 保留指数：
  2420;2420;2446;2422.5;2418.3;2446.8;2446.8;2430;2415;2448.5

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：在哺乳期间，偶尔的小剂量服用克立马丁是可以接受的。较大剂量或更长时间的使用可能会导致婴儿出现嗜睡和其他副作用，或者减少乳汁供应，尤其是与伪麻黄碱等拟交感神经药联合使用时，或者在哺乳尚未稳定建立之前。许多女性在最后一次喂奶后睡前单次给药可能就足够了，并且这样可以最小化药物的影响。首选的非嗜睡性抗组胺药作为替代品。 对哺乳婴儿的影响：一名正在服用克立马丁、苯妥英和卡马西平的母亲的10周大哺乳婴儿出现了嗜睡、拒绝进食、烦躁不安和高音哭泣。这些副作用可能是由母乳中的克立马丁引起的，但其他药物也可能有所贡献。 在一项电话随访研究中，母亲报告称，暴露于各种抗组胺药的婴儿中有10%出现了烦躁和肠绞痛症状，1.6%的婴儿出现了嗜睡。没有任何反应需要医疗关注。 对哺乳和母乳的影响：相对高剂量的抗组胺药通过注射给药可以减少非哺乳期妇女和早期产后期妇女的基础血清催乳素。然而，哺乳诱导的催乳素分泌不受产后母亲抗组胺药预处理的影响。尚未研究较低口服剂量的抗组胺药是否对血清催乳素有相同的影响，或者对催乳素的影响是否对哺乳成功有任何后果。在已建立哺乳的母亲中，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Small occasional doses of clemastine are acceptable during breastfeeding. Larger doses or more prolonged use may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. Single bedtime doses after the last feeding of the day may be adequate for many women and will minimize any effects of the drug. The nonsedating antihistamines are preferred alternatives. ◉ Effects in Breastfed Infants:A 10-week-old breastfed infant whose mother was taking clemastine, phenytoin and carbamazepine was drowsy, refused to feed, was irritable, and had high-pitched crying. These side effects were possibly caused by clemastine in breastmilk, but the other drugs could also have contributed. In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention. ◉ Effects on Lactation and Breastmilk:Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 海关编码：
  2933990090

制备方法与用途

用途：抗组胺药适用于过敏性鼻炎、荨麻疹、湿疹以及其他过敏性皮肤疾病。

反应信息

• 作为反应物：
  描述：

  硫氰酸铵 、 ammonium molybdate 、 2-[2-[1-(4-氯苯基)-1-苯基-乙氧基]乙基]-1-甲基吡咯烷 在 盐酸 、 维生素 C 作用下， 以 盐酸 、 水 为溶剂， 生成 (clemastine(+H))[Mo(thiocyanate)6]
  参考文献：
  名称：

  分光光度法测定其药物制剂中的某些组胺H1拮抗剂药物。

  摘要：

  已经开发了两种快速，简单和灵敏的萃取分光光度法，用于测定三种及其在药物制剂中的组胺H1拮抗剂药物，例如氯苯氧胺盐酸盐（CPX），苯海拉明盐酸盐（DPH）和氯马汀（CMT）。第一种方法取决于硫氰酸钼（V）离子（方法A）与所引用药物的反应形成稳定的离子对络合物，该络合物可通过二氯甲烷萃取，在λ（最大）470nm处进行比色测定。第二种方法是基于在酸性介质中形成一种以茜素红S作为显色剂的离子缔合络合物（方法B），然后将其萃取到氯仿中。对于（DPH或CMT）和CPX，络合物分别在425和426nm处具有最大吸光度。Beer-Lambert图的回归分析显示，硫氰酸钼（V）（方法A）和茜素红S（方法B）的浓度范围分别为5.0-40和5-70microgmL（-1）良好。为了进行更准确的分析，计算了林宝最佳浓度范围。计算了摩尔吸光度，Sandell灵敏度，检测和定量限。将该程序应用于各种药物制剂的分析，可

  DOI：

  10.1016/j.saa.2007.03.040

文献信息

• SUBSTITUTED BENZHYDRYLETHERS
  申请人：Gant Thomas G.

  公开号：US20090203763A1

  公开（公告）日：2009-08-13

  Disclosed herein are substituted benzhydrylethers of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of their use thereof.

  本文揭示了式I的取代苯基乙醚，其制备方法，药物组合物以及它们的使用方法。
• Compositions of antiallergics and antihistamines and methods for their use
  申请人：ALCON LABORATORIES, INC.

  公开号：EP0433766A1

  公开（公告）日：1991-06-26

  Compositions of an antiallergic compound and an antihistamine for preventing and treating ophthalmic allergic response are disclosed. Methods for preventing and treating ophthalmic allergic response with the compositions are also disclosed.

  本发明公开了用于预防和治疗眼科过敏反应的抗过敏化合物和抗组胺剂的组合物。还公开了使用该组合物预防和治疗眼科过敏反应的方法。
• Pharmaceutical composition of a pde4 or a pde3/4 inhibitor and a histamine receptor antagonist
  申请人：Nycomed GmbH

  公开号：EP1849468A2

  公开（公告）日：2007-10-31

  The invention relates to the combined administration of PDE4 or PDE3/4 inhibitors and histamine receptor antagonists for the treatment of respiratory diseases.

  本发明涉及联合使用 PDE4 或 PDE3/4 抑制剂和组胺受体拮抗剂治疗呼吸系统疾病。
• Directed differentiation of oligodendrocyte precursor cells to a myelinating cell fate
  申请人：The Scripps Research Institute

  公开号：US10660899B2

  公开（公告）日：2020-05-26

  The present invention provides methods of inducing differentiation of oligodendrocyte progenitor cells to a mature myelinating cell fate with a neurotransmitter receptor modulating agent. The present invention also provides methods of stimulating increased myelination in a subject in need thereof by administering said neurotransmitter receptor modulating agent. Methods of treating a subject having a demyelinating disease using a neurotransmitter receptor modulating agent are also provided.

  本发明提供了用神经递质受体调节剂诱导少突胶质祖细胞向成熟髓鞘细胞命运分化的方法。本发明还提供了通过施用所述神经递质受体调节剂刺激有需要的受试者增加髓鞘化的方法。本发明还提供了使用神经递质受体调节剂治疗脱髓鞘疾病的方法。
• Delivery of antihistamines through an inhalation route
  申请人：——

  公开号：US20030015189A1

  公开（公告）日：2003-01-23

  The present invention relates to the delivery of antihistamines through an inhalation route. Specifically, it relates to aerosols containing antihistamines that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of an antihistamine. In a method aspect of the present invention, an antihistamine is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of an antihistamine, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering an antihistamine through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of an antihistamine; and, b) a device that forms an antihistamine containing aerosol from the composition, for inhalation by the mammal.

  本发明涉及通过吸入途径给药抗组胺剂。具体地说，它涉及用于吸入疗法的含有抗组胺剂的气雾剂。在本发明的一个组合物方面，气雾剂包含按重量计至少含有5%抗组胺剂的颗粒。在本发明的一个方法方面，通过吸入途径向哺乳动物递送抗组胺剂。该方法包括：a)加热组合物，其中组合物包含按重量计至少5%的抗组胺剂，以形成蒸气；b)使蒸气冷却，从而形成包含颗粒的冷凝气溶胶，由哺乳动物吸入。在本发明的一个试剂盒方面，提供了一种通过吸入途径向哺乳动物递送抗组胺剂的试剂盒，该试剂盒包括：a) 一种组合物，按重量计至少含有 5%的抗组胺剂；b) 一种装置，从组合物中形成含有抗组胺剂的气溶胶，供哺乳动物吸入。

表征谱图