卡巴斯汀 | 79516-68-0

• 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 - 有机杂环化合物 - 哌啶类
• 中文名称: 卡巴斯汀
• 英文名称: (3S,4R)-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenylpiperidin-1-ium-4-carboxylate
• CAS: 79516-68-0
• 化学式: C26H29FN2O2
• 分子量: 420.5
• InChiKey: ZCGOMHNNNFPNMX-YHYDXASRSA-N

物化性质

• 沸点：
  589.9±50.0 °C(Predicted)
• 密度：
  1.23
• 物理描述：
  Solid
• 溶解度：
  >0.5 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.3
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

大部分没有变化。10到20%代谢成Levocabastine的酰基葡萄糖醛酸。

Mostly unchanged. 10 to 20% is metabolized to the acylglucuronide of levocabastine.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：由于眼部吸收有限，预计左卡巴斯汀不会对哺乳婴儿产生任何不良反应。为了显著减少使用眼药水后药物到达母乳的量，可以在眼角处对泪点施加压力1分钟或更长时间，然后用吸收性纸巾去除多余的溶液。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到关于左卡巴斯汀的相关已发布信息。在一项电话随访研究中，母亲报告有10%的婴儿在接触各种抗组胺药后出现烦躁和肠绞痛症状，1.6%的婴儿出现嗜睡。所有反应均未需要医疗关注。 ◉ 对泌乳和母乳的影响：在非哺乳期妇女和产后早期妇女中，通过注射给予相对高剂量的抗组胺药可以降低基础血清催乳素。然而，吸吮诱导的催乳素分泌不会受到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母乳喂养成功有任何影响。在已建立泌乳的母亲中，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Because absorption from the eye is limited, levocabastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants:Relevant published information on levocabastine was not found as of the revision date. 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)

吸收、分配和排泄

• 吸收

滴入眼睛后，莱沃卡巴汀会被系统吸收，尽管吸收水平较低。

After instillation in the eye, levocabastine is systemically absorbed, albeit at low levels.

来源:DrugBank

制备方法与用途

化学性质：盐酸左卡巴斯汀（Levocabastine Hydrochloride），分子式为 C26H29FN2O2·HCl，CAS号为 79547-78-7。该物质为结晶状固体，熔点在 298-299℃。

用途：盐酸左卡巴斯汀是一种组胺 H1 受体拮抗剂，具有高选择性和强活性。主要用于治疗过敏性鼻炎和过敏性结膜炎。

生产方法：首先使化合物(I)与化合物(II)反应生成化合物(Ⅲ)，再通过还原得到化合物(Ⅳ)，最后进行水解得到盐酸左卡巴斯汀。

文献信息

• Pteridinone derivatives as PI3-kinases inhibitors
  申请人：Boehringer Ingelheim Pharma GmbH & Co. KG

  公开号：EP1953163A1

  公开（公告）日：2008-08-06

  New compounds of formula 1 are provided which by virtue of their pharmaceutical activity as PI3-kinase modulators may be used in the therapeutic field for the treatment of inflammatory or allergic diseases. Examples of these include inflammatory and allergic respiratory complaints, inflammatory diseases of the gastro-intestinal tract and motor apparatus, inflammatory and allergic skin diseases, inflammatory eye diseases, diseases of the nasal mucosa, inflammatory or allergic conditions involving autoimmune reactions or inflammations of the kidney.

  根据其作为PI3-激酶调节剂的药理活性，提供了公式1的新化合物，可用于治疗炎症或过敏性疾病的治疗领域。 这些例子包括炎症和过敏性呼吸道疾病，胃肠道和运动器官的炎症性疾病，炎症性和过敏性皮肤疾病，炎症性眼病，鼻黏膜疾病，涉及自身免疫反应或肾脏炎症的炎症性或过敏性疾病。
• Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20160095858A1

  公开（公告）日：2016-04-07

  The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

  本发明涉及一种具有以下化学式I的化合物： 或其药用可接受的盐，其中R 1 ，R 2 ，R 3 ，W，X，Y，Z，n，o，p和q在此处定义，用于治疗CFTR介导的疾病，如囊性纤维化。本发明还涉及药物组合物、治疗方法和相关工具包。
• HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING SAID COMPOUNDS, USE THEREOF AND PROCESSES FOR THE PREPARATION THEREOF
  申请人：HECKEL Armin

  公开号：US20130157981A1

  公开（公告）日：2013-06-20

  The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

  本发明涉及一般式（I）的化合物，以及其互变异构体和盐，特别是其与无机或有机酸和碱形成的药用可接受盐，具有有价值的药理特性，特别是对上皮钠通道具有抑制作用，以及其用于治疗疾病，特别是肺部和气道疾病的用途。
• [EN] HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING SAID COMPOUNDS, USE THEREOF AND PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES, MÉDICAMENTS CONTENANT LESDITS COMPOSÉS, UTILISATION DE CEUX-CI ET PROCÉDÉS POUR LA PRÉPARATION DE CEUX-CI
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013092674A1

  公开（公告）日：2013-06-27

  The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

  本发明涉及一般式(I)的化合物，以及其互变异构体和盐，特别是其与无机或有机酸和碱形成的药用盐，具有有价值的药理特性，特别是对上皮钠通道具有抑制作用，其用于治疗疾病，特别是肺部和气道疾病。
• Prodrugs containing novel bio-cleavable linkers
  申请人：Satyam Apparao

  公开号：US20060046967A1

  公开（公告）日：2006-03-02

  The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

  本发明提供了公式(I)的化合物或其药用可接受的盐。本发明还提供了包含一个或多个公式I的化合物或其中间体以及一个或多个药用可接受的载体、车辆或稀释剂的药物组合物。本发明进一步提供了包括制备方法和使用方法在内的前药，包括释放一氧化氮的前药、双前药和相互前药，由公式I的化合物组成。