Aclidinium | 727649-81-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: Aclidinium
• 英文别名: [(3R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate
• CAS: 727649-81-2
• 化学式: C26H30NO4S2+
• 分子量: 484.7
• InChiKey: ASMXXROZKSBQIH-VITNCHFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

阿clidinium溴化物的主要代谢途径是水解，这种水解在血浆中的酯酶通过化学和酶促方式进行。阿clidinium溴化物迅速且广泛地被水解为其醇和二噻吩基乙醇酸衍生物，这些衍生物既不与毒蕈碱受体结合，也没有药理活性。

The major route of metabolism of aclidinium bromide is hydrolysis, which occurs both chemically and enzymatically by esterases in the plasma. Aclidinium bromide is rapidly and extensively hydrolyzed to its alcohol and dithienylglycolic acid derivatives, neither of which binds to muscarinic receptors and are pharmacologically inactive.

来源:DrugBank

毒理性

• 肝毒性

与其他抗胆碱能药物一样，阿立哌隆并未与肝酶升高或临床上明显的肝脏损伤发生关联。其安全性较高的主要原因可能与通过吸入器给药的抗胆碱能药物的低系统吸收和暴露有关。 在抗胆碱能药物概述部分之后，将提供关于抗胆碱能药物安全性和潜在肝毒性的参考资料。 药物类别：抗胆碱能药物

Like other anticholinergic agents, aclidinium has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. A major reason for its safety may relate to the low systemic absorption and exposure associated with anticholinergic agents administered by inhaler. References on the safety and potential hepatotoxicity of anticholinergics are given together after the Overview section on the Anticholinergic Agents. Drug Class: Anticholinergic Agents

来源:LiverTox

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：尽管没有关于aclidinium在哺乳期间使用的已发表数据，但由于迅速水解为无活性代谢物，它会产生较低的母体血清水平。母亲吸入aclidinium对哺乳婴儿的风险很小。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发表信息。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发表信息。

◉ Summary of Use during Lactation:Although no published data exist on the use of aclidinium during breastfeeding, it produces low maternal serum levels because of rapid hydrolysis to inactive metabolites. The risk to the breastfed infant of maternal aclidinium inhalation is small. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 吸收

生物利用度，健康受试者 = 6%；达峰时间，健康受试者 = 10分钟；达到稳态时间，健康受试者 = 2天；

Bioavailability, healthy subjects = 6%; T max, healthy subjects = 10 minutes; Time to steady state, healthy subjects = 2 days;

来源:DrugBank

吸收、分配和排泄

• 消除途径

静脉给药的放射性标记的阿clidinium溴化物被给予健康志愿者，并广泛代谢，其中1%以未改变的阿clidinium形式排出。大约54%至65%的放射性物质通过尿液排出，20%至33%的剂量通过粪便排出。综合结果表明，几乎整个阿clidinium溴化物剂量通过水解消除。在干粉吸入后，阿clidinium通过尿液的排出量约为剂量的0.09%。

Intravenously administered radiolabelled aclidinium bromide was administered to healthy volunteers and was extensively metabolized with 1% excreted as unchanged aclidinium. Approximately 54% to 65% of the radioactivity was excreted in urine and 20% to 33% of the dose was excreted in feces. The combined results indicated that almost the entire aclidinium bromide dose was eliminated by hydrolysis. After dry powder inhalation, urinary excretion of aclidinium is about 0.09% of the dose.

来源:DrugBank

吸收、分配和排泄

• 分布容积

静脉给药后，分布容积为300升。

Following IV administration, the volume of distribution is 300 L

来源:DrugBank

吸收、分配和排泄

• 清除

总清除率，静脉注射剂量，年轻健康受试者 = 170 L/h（个体间差异为36%）

Total clearance, IV dose, young healthy subjects = 170 L/h (inter-individual variability of 36%)

来源:DrugBank

文献信息

• COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
  申请人：CHIESI FARMACEUTICI S.P.A.

  公开号：US20180016267A1

  公开（公告）日：2018-01-18

  Compounds of formula I defined herein act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases.

  本处定义的I式化合物既作为肌肉收缩受体拮抗剂，又作为β2肾上腺素受体激动剂，可用于预防和/或治疗支气管阻塞或炎症性疾病。
• Pharmaceutical Product Comprising a P38 Kinase Inhibitor and a Second Active Ingredient
  申请人：Cooper Anne Elizabeth

  公开号：US20120028941A1

  公开（公告）日：2012-02-02

  The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclopropyl-3-fluoro-4-methyl-5[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a β2 adrenoceptor agonist; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DPI antagonist; an Histone Deacetylase activator; an IKK2 kinase inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; a MABA compound; an MPO inhibitor; a muscarinic antagonist; a PDE4 inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

  该发明提供了一种制药产品、套装或组合物，包括第一活性成分N-环丙基-3-氟-4-甲基-5-[3-[[1-[2-[2-(甲氨基)乙氧基]苯基]环丙基]氨基]-2-氧代-1(2H)-吡嗪基]-苯甲酰胺或其盐，以及从以下选取的第二活性成分：非类固醇糖皮质激素受体（GR受体）激动剂；抗氧化剂；β2肾上腺素受体激动剂；CCR1拮抗剂；趋化因子拮抗剂（非CCR1）；皮质类固醇；CRTh2拮抗剂；DPI拮抗剂；组蛋白去乙酰化酶激活剂；IKK2激酶抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MABA化合物；MPO抑制剂；毛细血管抗药性剂；PDE4抑制剂；PPARγ激动剂；蛋白酶抑制剂；他汀类药物；前列腺素拮抗剂；扩血管剂；或者ENAC拮抗剂（上皮钠通道拮抗剂）；以及其在呼吸系统疾病治疗中的用途。
• [EN] COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY<br/>[FR] COMPOSÉS AYANT UNE ACTIVITÉ D'ANTAGONISTE DES RÉCEPTEURS MUSCARINIQUES ET D'AGONISTE DES RÉCEPTEURS ADRÉNERGIQUES BÊTA2
  申请人：CHIESI FARM SPA

  公开号：WO2017093208A1

  公开（公告）日：2017-06-08

  The present invention relates to compounds acting both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists, to processes for their preparation, to compositions comprising them, to therapeutic uses and combinations with other pharmaceutical active ingredients.

  这项发明涉及既作为肌肉胆碱受体拮抗剂又作为β2肾上腺素受体激动剂的化合物，涉及它们的制备方法，包含它们的组合物，治疗用途以及与其他药用活性成分的组合。
• [EN] COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY<br/>[FR] COMPOSÉS AYANT UNE ACTIVITÉ ANTAGONISTE DU RÉCEPTEUR MUSCARINIQUE ET AGONISTE DU RÉCEPTEUR BÊTA2 ADRÉNERGIQUE
  申请人：CHIESI FARMA SPA

  公开号：WO2014086924A1

  公开（公告）日：2014-06-12

  The present invention relates to compounds acting both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists, to processes for their preparation, to compositions comprising them, to therapeutic uses and combinations with other pharmaceutical active ingredients.

  这项发明涉及既作为肌肉胆碱受体拮抗剂又作为β2肾上腺素受体激动剂的化合物，涉及它们的制备方法，包含它们的组合物，治疗用途以及与其他药用活性成分的组合。
• [EN] COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY<br/>[FR] COMPOSÉS AYANT UNE ACTIVITÉ ANTAGONISTE DES RÉCEPTEURS MUSCARINIQUES ET UNE ACTIVITÉ AGONISTE DES RÉCEPTEURS ADRÉNERGIQUE BÊTA-2
  申请人：CHIESI FARMA SPA

  公开号：WO2012168349A1

  公开（公告）日：2012-12-13

  The present invention relates to compounds of general formula (I), acting both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists, to processes for their preparation, to compositions comprising them, to therapeutic uses and combinations with other pharmaceutical active ingredients.

  这项发明涉及一般式(I)的化合物，它们既作为肌肉收缩受体拮抗剂，又作为β2肾上腺素受体激动剂，涉及它们的制备方法，包含它们的组合物，治疗用途以及与其他药用活性成分的组合。