2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide | 862540-80-5

• 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: 2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide
• 英文别名: 2-[3-[2-[[(2R)-2-[tert-butyl(dimethyl)silyl]oxy-2-[4-hydroxy-3-(methanesulfonamido)phenyl]ethyl]amino]-2-methylpropyl]phenyl]-N-[[3-(4-hydroxyphenyl)phenyl]methyl]acetamide
• CAS: 862540-80-5
• 化学式: C₄₀H₅₃N₃O₆SSi
• 分子量: 732.029
• InChiKey: POWWWTCEVARVGN-QNGWXLTQSA-N

物化性质

• 密度：
  1.183±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.67
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  145
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide 在 氟化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 生成 (R)-2-(3-{2-[2-(4-benzyloxy-3-methanesulfonamidophenyl)-2-hydroxyethylamino]-2-methylpropyl}phenyl)-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide hemifumarate
  参考文献：
  名称：

  Sulfonamide derivatives for the treatment of diseases

  摘要：

  该发明涉及公式（1）的化合物，以及用于制备、用于制备的中间体、含有和使用这些衍生物的组合物的过程。根据本发明的化合物在许多疾病、紊乱和状况中具有用途，特别是在炎症性、过敏性和呼吸系统疾病、紊乱和状况中。

  公开号：

  US20050182091A1
• 作为产物：
  描述：

  N-(5-乙酰基-2-(苄氧基)苯基)甲磺酰胺 在 咪唑 、 硼酸三甲酯 、 dimethyl sulfide borane 、 20% palladium hydroxide on charcoal 、 甲酸铵 、 tetra-N-butylammonium tribromide 、 (R)-(+)-alpha,alpha-二苯基脯氨醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 146.75h， 生成 2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide
  参考文献：
  名称：

  Development of an Enabling Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist

  摘要：

  The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6 center dot HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.

  DOI：

  10.1021/op2001904

文献信息

• Sulfonamide derivatives for the treatment of diseases
  申请人：Brown Daniel Alan

  公开号：US20050182091A1

  公开（公告）日：2005-08-18

  The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

  该发明涉及公式（1）的化合物，以及用于制备、用于制备的中间体、含有和使用这些衍生物的组合物的过程。根据本发明的化合物在许多疾病、紊乱和状况中具有用途，特别是在炎症性、过敏性和呼吸系统疾病、紊乱和状况中。
• Inhalation by Design: Novel Ultra-Long-Acting β₂-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup
  作者：Paul A. Glossop、Charlotte A. L. Lane、David A. Price、Mark E. Bunnage、Russell A. Lewthwaite、Kim James、Alan D. Brown、Michael Yeadon、Christelle Perros-Huguet、Michael A. Trevethick、Nicholas P. Clarke、Robert Webster、Rhys M. Jones、Jane L. Burrows、Neil Feeder、Stefan C. J. Taylor、Fiona J. Spence

  DOI：10.1021/jm1005989

  日期：2010.9.23

  A novel series of potent and selective sulfonamide derived beta(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming, its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.
• [EN] PROCESS FOR THE PREPARATION OF SULFONAMIDE DERIVATIVES<br/>[FR] PROCEDE POUR LA PREPARATION DE DERIVES DE SULFONAMIDE
  申请人：PFIZER LTD

  公开号：WO2007010356A3

  公开（公告）日：2007-08-23
• Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist
  作者：Pieter D. de Koning、Nieves Castro、Iain R. Gladwell、Natalie A. Morrison、Ian B. Moses、Maninder S. Panesar、Alan J. Pettman、Nicholas M. Thomson

  DOI：10.1021/op2002408

  日期：2011.11.18

  The development of a practical, scalable route to PF-00610355 (8) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26. TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a. On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API (8) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.
• Development of an Enabling Route to PF-00610355: A Novel Inhaled β₂-Adrenoreceptor Agonist
  作者：Pieter D. de Koning、Iain R. Gladwell、Ian B. Moses、Maninder S. Panesar、Alan J. Pettman、Nicholas M. Thomson

  DOI：10.1021/op2001904

  日期：2011.11.18

  The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6 center dot HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.