milveterol | 652990-07-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: milveterol
• 英文别名: N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[2-[4-[[(2R)-2-hydroxy-2-phenylethyl]amino]phenyl]ethylamino]ethyl]phenyl]formamide
• CAS: 652990-07-3
• 化学式: C₂₅H₂₉N₃O₄
• 分子量: 435.523
• InChiKey: BMKINZUHKYLSKI-DQEYMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  114
• 氢给体数：
  6
• 氢受体数：
  6

制备方法与用途

Milveterol (GSK 159797) 是一种强效、选择性的长效β2肾上腺素受体激动剂，在细胞基质 assay 中的 pEC50 值为 10.2，表现出对 β2/β1 受体的选择性大于 300 倍。

反应信息

• 作为反应物：
  描述：

  milveterol 在 盐酸 作用下， 以 水 、 异丙醇 为溶剂， 反应 6.17h， 以70%的产率得到GSK159797
  参考文献：
  名称：

  [EN] CHEMICAL PROCESS AND NEW CRYSTALLINE FORM
  [FR] PROCESSUS CHIMIQUE ET NOUVELLE FORME CRISTALLINE

  摘要：

  本发明涉及以结晶盐形式制备β2肾上腺素受体激动剂。具体而言，本发明涉及制备化合物(I)的结晶盐，特别是结晶单盐酸盐。该发明还涉及化合物(Ia)的单盐酸盐的新结晶形式（多形态）以及其制备方法。

  公开号：

  WO2005095328A1
• 作为产物：
  描述：

  2-(4-氨基苯)乙胺 在 sodium tetrahydroborate 、 正丁基锂 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲苯 为溶剂， 生成 milveterol
  参考文献：
  名称：

  A multivalent approach to the discovery of long-acting β2-adrenoceptor agonists for the treatment of asthma and COPD

  摘要：

  A multivalent approach was applied to the design of long-acting inhaled beta(2)-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting beta(2)-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C-2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding Potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.072

文献信息

• Azabicycloalkane compounds
  申请人：——

  公开号：US20040242622A1

  公开（公告）日：2004-12-02

  This invention provides compounds of formula I: 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both &bgr; 2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

  这项发明提供了式I的化合物： 其中R1、R2、R3、R4、R5、R6和R7如规范中所定义，或其药用可接受盐、溶剂或立体异构体。本发明的化合物具有β2肾上腺素受体激动剂和肌碱受体拮抗剂活性。这些化合物对治疗肺部疾病，如慢性阻塞性肺病和哮喘，是有用的。
• 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。
• Quaternary ammonium compounds useful as muscarinic receptor antagonists
  申请人：Husfeld Craig

  公开号：US20080269190A1

  公开（公告）日：2008-10-30

  The invention provides compounds of the formula: in salt or zwitterionic form or a pharmaceutically acceptable salt thereof, wherein R 1-6 , a, Z and Q are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.

  该发明提供了以下公式的化合物：以盐或带电离子形式或其药用可接受盐的形式存在，其中R1-6、a、Z和Q如规范中定义。这些化合物是肌氨酸受体拮抗剂。该发明还提供含有这些化合物的药物组合物，制备这些化合物的方法以及使用这些化合物的方法，例如用于治疗慢性阻塞性肺疾病和哮喘等肺部疾病。
• Guanidine-containing compounds useful as muscarinic receptor antagonists
  申请人：Ji YuHua

  公开号：US20090069335A1

  公开（公告）日：2009-03-12

  The invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein R 1-3 , R 5-7 , a, X, Y, Y′, Y″, and Z are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.

  该发明提供了以下公式I的化合物或其药用盐，其中R1-3、R5-7、a、X、Y、Y'、Y"和Z如规范中所定义。这些化合物是肌氨酸受体拮抗剂。该发明还提供含有这些化合物的药物组合物，制备这些化合物的方法以及使用这些化合物治疗肺部疾病如慢性阻塞性肺疾病和哮喘的方法。
• AMIDINE-CONTAINING COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS
  申请人：Ji YuHua

  公开号：US20090170870A1

  公开（公告）日：2009-07-02

  The invention relates to compounds of formula I: or a pharmaceutically acceptable salt thereof, where R 1-3 , R 5 , R 7 , a, b, Q, X, X′, X″, Y, Z, and Ar are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also relates to pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.

  该发明涉及以下式I的化合物：或其药用可接受的盐，其中R1-3、R5、R7、a、b、Q、X、X′、X″、Y、Z和Ar如规范中所定义。这些化合物是肌肉胆碱受体拮抗剂。该发明还涉及含有这些化合物的药物组合物，制备这些化合物的方法以及利用这些化合物治疗肺部疾病（如慢性阻塞性肺疾病和哮喘）等方法。