biphenyl-2-ylcarbamic acid 1-[2-(4-formylbenzoylamino)ethyl]piperidin-4-yl ester | 864760-29-2

• 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: biphenyl-2-ylcarbamic acid 1-[2-(4-formylbenzoylamino)ethyl]piperidin-4-yl ester
• 英文别名: [1-[2-[(4-formylbenzoyl)amino]ethyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate
• CAS: 864760-29-2
• 化学式: C₂₈H₂₉N₃O₄
• 分子量: 471.556
• InChiKey: UYLKAWVBXBKHDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  biphenyl-2-ylcarbamic acid 1-[2-(4-formylbenzoylamino)ethyl]piperidin-4-yl ester 在 triethylamine tris(hydrogen fluoride) 作用下， 反应 3.0h， 生成 biphenyl-2-ylcarbamic Acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzoylamino)ethyl]piperidin-4-yl ester ditrifluoroacetate
  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
• 作为产物：
  描述：

  异氰酸2-联苯酯 在 palladium 10% on activated carbon 、 甲酸铵 、 二甲基亚砜 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 27.25h， 生成 biphenyl-2-ylcarbamic acid 1-[2-(4-formylbenzoylamino)ethyl]piperidin-4-yl ester
  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

• 一种联苯衍生物及其制备方法和在医药上的用途
  申请人：四川海思科制药有限公司

  公开号：CN110590776A

  公开（公告）日：2019-12-20

  本发明涉及一种联苯衍生物及其制备方法和在医药上的用途，所述联苯衍生物为一种通式(I)或(II)所示的化合物或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐、共晶或前药，以及制备方法和在制备用于治疗气道阻塞性疾病药物中的应用,其中通式(I)或(II)所示的化合物如下所示：其中，各取代基的定义与说明书中一致。
• Biphenyl compounds useful as muscarinic receptor antagonists
  申请人：Ji Yu-Hua

  公开号：US20060281740A1

  公开（公告）日：2006-12-14

  The invention provides compounds of formula I: wherein a, b, c, m, s, t, W, Z, Ar, R 1 , R 2 , R 3 , R 6 , and R 7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

  这项发明提供了化合物的公式I：其中a、b、c、m、s、t、W、Z、Ar、R1、R2、R3、R6和R7如规范中定义。公式I的化合物是肌氨酸受体拮抗剂。该发明还提供了含有这些化合物的药物组合物、制备这些化合物的过程和中间体以及使用这些化合物治疗肺部疾病的方法。
• BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS
  申请人：JI Yu-Hua

  公开号：US20100197667A1

  公开（公告）日：2010-08-05

  The invention provides compounds of formula I: wherein a, b, c, m, s, t, W, Z, Ar, R 1 , R 2 , R 3 , R 6 , and R 7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

  该发明提供了公式I的化合物：其中a、b、c、m、s、t、W、Z、Ar、R1、R2、R3、R6和R7如规范中所定义。公式I的化合物是肌动力受体拮抗剂。该发明还提供了含有这种化合物的药物组合物，制备这种化合物的过程和中间体以及使用这种化合物治疗肺部疾病的方法。
• US7265133B2
  申请人：——

  公开号：US7265133B2

  公开（公告）日：2007-09-04
• US7728144B2
  申请人：——

  公开号：US7728144B2

  公开（公告）日：2010-06-01