methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate | 876126-21-5

• 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: methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate
• 英文别名: Methyl 4-(3-(4-(([1,1'-biphenyl]-2-ylcarbamoyl)oxy)piperidin-1-yl)propanamido)-5-chloro-2-methoxybenzoate；methyl 5-chloro-2-methoxy-4-[3-[4-[(2-phenylphenyl)carbamoyloxy]piperidin-1-yl]propanoylamino]benzoate
• CAS: 876126-21-5
• 化学式: C₃₀H₃₂ClN₃O₆
• 分子量: 566.054
• InChiKey: LLZOGPDYKURPND-UHFFFAOYSA-N

物化性质

• 沸点：
  722.8±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate 以21的产率得到biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-hydroxymethyl-5-methoxy-phenylcarbamoyl)ethyl]piperidin-4-yl ester
  参考文献：
  名称：

  Library of biphenyl derivatives

  摘要：

  本发明提供了一种公式I的联苯衍生物库：1其中R1、R2、R3、R4、R5、R6、R7、W、a、b和c如规范中所定义，或其盐或立体异构体。该库对于鉴定具有β2肾上腺素能受体激动剂和肌动蛋白受体拮抗剂活性的化合物非常有用。因此，本发明还提供了评估或筛选联苯衍生物库以鉴定具有这种双重功能活性的化合物的方法。

  公开号：

  US20040209915A1
• 作为产物：
  描述：

  异氰酸2-联苯酯 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 40.0h， 生成 methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate
  参考文献：
  名称：

  Discovery of (R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1′-Biphenyl]-2-ylcarbamate (TD-5959, GSK961081, Batefenterol): First-in-Class Dual Pharmacology Multivalent Muscarinic Antagonist and β₂ Agonist (MABA) for the Treatment of Chronic Obstructive Pulmonary Disease (COPD)

  摘要：

  Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and beta(2) agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

  DOI：

  10.1021/jm501915g

文献信息

• Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
  申请人：Mammen Mathai

  公开号：US20050113417A1

  公开（公告）日：2005-05-26

  The invention is directed to compounds of formula I: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7a , R 7b , W, G 1 , G 2 , a, b, c, d and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  这项发明涉及到以下式I的化合物：其中R1、R2、R3、R4、R5、R6、R7a、R7b、W、G1、G2、a、b、c、d和m如规范中所定义，或其药学上可接受的盐、溶剂或立体异构体。该发明还涉及包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的过程和中间体。
• Biphenyl derivatives
  申请人：——

  公开号：US20040167167A1

  公开（公告）日：2004-08-26

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

  这项发明提供了式I中的联苯衍生物：其中R1、R2、R3、R4、R5、R6、R7、W、a、b和c如规范中定义，或其药学上可接受的盐、溶剂或立体异构体。本发明的联苯衍生物具有β2肾上腺素受体激动剂和肌力抑制剂活性，因此，这种联苯衍生物可用于治疗肺部疾病，如慢性阻塞性肺疾病和哮喘。
• Process for the Preparation of a Biphenyl-2-Yl carbamic Acid Ester
  申请人：Edney Dean David

  公开号：US20120046469A1

  公开（公告）日：2012-02-23

  A novel process for the preparation of the compound of formula (II): which process comprises reacting a compound of formula (VI): with a compound of formula (IV): in a suitable solvent.

  一种制备化合物II的新工艺：该工艺包括在适当溶剂中将化合物VI与化合物IV反应。
• Crystalline form of a biphenyl compound
  申请人：Chao S. Robert

  公开号：US20060035931A1

  公开（公告）日：2006-02-16

  The invention provides a crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also provides pharmaceutical compositions comprising such a salt or prepared using such a salt; processes and intermediates for preparing such a salt; and methods of using such a salt to treat a pulmonary disorder.

  该发明提供了苯并二氯甲酸盐的结晶1,2-乙二磺酸盐1-[2-（2-氯-4-[(R)-2-羟基-2-(8-羟基-2-氧代-1,2-二氢喹啉-5-基)乙基氨基]甲基}-5-甲氧基苯基羰基）乙基]哌啶-4-基酯或其溶剂结晶体。该发明还提供了包含该盐或使用该盐制备的药物组合物；制备该盐的过程和中间体；以及使用该盐治疗肺部疾病的方法。
• Compound
  申请人：Glaxo Group Limited

  公开号：US07960551B2

  公开（公告）日：2011-06-14

  A succinic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof, for use in treating pulmonary disorders.

  一种琥珀酸盐，其为联苯基氨甲酸1-[2-(2-氯-4-[(R)-2-羟基-2-(8-羟基-2-氧代-1,2-二氢喹啉-5-基)乙基]氨甲基}-5-甲氧基苯基甲酰)乙基]哌啶-4-基酯或其溶剂合物，用于治疗肺部疾病。