福莫特罗 | 67346-49-0

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 福莫特罗
• 英文名称: (R,R)-formoterol
• 英文别名: (-)-Formoterol；(R,R)-N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formaldehyde；N-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino}ethyl]phenyl}formamide；3-formamido-4-hydroxy-α-[[N-(p-methoxy-α-methylphenethyl)amino]methyl]benzyl alcohol；(R,R)-N-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide；Arformoterol；N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide
• CAS: 67346-49-0
• 化学式: C₁₉H₂₄N₂O₄
• 分子量: 344.411
• InChiKey: BPZSYCZIITTYBL-YJYMSZOUSA-N

物化性质

• 熔点：
  73-75 °C
• 沸点：
  603.2±55.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)
• 溶解度：
  25℃：二甲基亚砜
• 物理描述：
  Solid
• 蒸汽压力：
  5.0X10-14 mm Hg at 25 °C /Estimated/

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  90.8
• 氢给体数：
  4
• 氢受体数：
  5

ADMET

代谢

阿福特罗在八名健康受试者口服35微克放射性标记阿福特罗后几乎完全代谢。阿福特罗与葡萄糖醛酸的直接结合是主要的代谢途径。O-脱甲基是一种次要的代谢途径，由CYP酶CYP2D6和CYP2C19催化。

Arformoterol was almost entirely metabolized following oral administration of 35 mcg of radiolabeled arformoterol in eight healthy subjects. Direct conjugation of arformoterol with glucuronic acid was the major metabolic pathway. O-Desmethylation is a secondary route catalyzed by the CYP enzymes CYP2D6 and CYP2C19.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：阿福特罗是长效β-2肾上腺素能激动剂，福莫特罗的R-对映体。尽管没有关于在母乳喂养期间通过吸入使用阿福特罗的已发表数据，但相关药物特布他林的数据表明，预计很少有药物会分泌到母乳中。几篇综述的作者和一个专家小组认为，由于吸入支气管扩张剂后生物利用度低和母体血清水平低，因此在哺乳期间使用是可接受的。 ◉ 对哺乳婴儿的影响：截至修订日期，没有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，没有找到相关的已发表信息。

◉ Summary of Use during Lactation:Arformoterol is the R-enantiomer of the long-acting beta-2 adrenergic agonist, formoterol. Although no published data exist on the use of arformoterol by inhalation during lactation, data from the related drug, terbutaline, indicate that very little is expected to be excreted into breastmilk. The authors of several reviews and an expert panel agree that use of inhaled bronchodilators is acceptable during breastfeeding because of the low bioavailability and maternal serum levels after use. ◉ 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)

毒理性

• 蛋白质结合

阿福特罗尔与人体血浆蛋白的体外结合率为52-65%，在放射性阿福特罗尔浓度为0.25、0.5和1.0 ng/mL时。

The binding of arformoterol to human plasma proteins in vitro was 52-65% at concentrations of 0.25, 0.5 and 1.0 ng/mL of radiolabeled arformoterol.

来源:DrugBank

吸收、分配和排泄

• 吸收

在患有慢性阻塞性肺病（COPD）的患者中，每日两次给药14天后，平均血浆峰浓度（Cmax）为4.3皮克/毫升，0-12小时药时曲线下面积（AUC0-12h）为34.5皮克·小时/毫升。血浆达到峰浓度的时间（Tmax）大约为0.5小时。

In patients with COPD, the mean peak plasma concentration (Cmax) and AUC0-12h following twice daily administration for 14 days were 4.3 pg/mL and 34.5 pg.hr/mL, respectively. The time to peak plasma concentration (Tmax) was approximately 0.5 hours.

来源:DrugBank

吸收、分配和排泄

• 消除途径

在给八名健康受试者单次口服阿福特罗尔后，48小时内，63%的给药剂量在尿液中回收，11%在粪便中回收。14天后，总共回收了89%的总剂量 - 67%在尿液中，22%在粪便中 - 尿液中大约有1%保持不变。

Following the administration of a single oral dose of arformoterol to eight healthy subjects, 63% of the administered dose was recovered in the urine and 11% in the feces within 48 hours. After 14 days, a total of 89% of the total dose had been recovered - 67% in the urine and 22% in the feces - with approximately 1% remaining unchanged in the urine.

来源:DrugBank

吸收、分配和排泄

• 清除

在健康的男性受试者中，单次口服阿福特罗尔的清除率为8.9 L/h。

In healthy male subjects, the clearance of a single oral dose of arformoterol was 8.9 L/h.

来源:DrugBank

安全信息

• 储存条件：
  室温

制备方法与用途

福莫特罗（阿福莫特罗）是一种β2肾上腺素受体激动剂。

反应信息

• 作为反应物：
  描述：

  福莫特罗 生成 arformoterol tartrate
  参考文献：
  名称：

  Drugs Fut. 2006, 31, 944

  摘要：

  DOI：
• 作为产物：
  描述：

  甲酰胺,N-[5-[(1R)-1-羟基-2-[[(1R)-1-甲基-2-(4-甲氧苯基)乙基](苯基甲基)氨基]乙基]-2-(苯基甲氧基)苯基]- 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 生成 福莫特罗
  参考文献：
  名称：

  PROCESSES FOR PREPARING SUBSTANTIALLY PURE ARFORMOTEROL AND ITS INTERMEDIATES

  摘要：

  本文提供了改进的、便捷的和在工业上具有优势的过程，用于制备N-[2-羟基-5-[(1R)-1-羟基-2-[[(1R)-2-(4-甲氧基苯基)-1-甲基乙基]氨基]乙基]苯甲酰胺（阿福莫特罗）或其药用可接受的盐，产率高，纯度高。此外，本文还提供了一种改进的、在工业上具有优势的过程，用于制备基本对映纯的阿福莫特罗中间体(R)-4-甲氧基-α-甲基-N-(苯甲基)苯乙胺。

  公开号：

  US20110313199A1

文献信息

• DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160221965A1

  公开（公告）日：2016-08-04

  The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.

  本申请涉及新颖的2,5-二取代6-(三氟甲基)嘧啶-4(3H)-酮衍生物，其制备方法，其单独或与其他药物联合用于治疗和/或预防疾病，以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防心血管、肾脏、炎症和纤维化疾病。
• [EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
  申请人：GALLEON PHARMACEUTICALS INC

  公开号：WO2009151744A1

  公开（公告）日：2009-12-17

  The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.

  本发明涉及基于巯基和S-亚硝基巯基的SNO化合物及其衍生物，以及它们在治疗正常呼吸控制缺失方面的用途，包括治疗与睡眠、肥胖、某些药物和其他医疗状况相关的呼吸暂停和低通气。
• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。