rac-(2S,4R,5R)-2-isobutyl-1-(3-methoxy-4-tert-butylbenzoyl)-4-hydroxymethyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid 2-tert-butyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: rac-(2S,4R,5R)-2-isobutyl-1-(3-methoxy-4-tert-butylbenzoyl)-4-hydroxymethyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid 2-tert-butyl ester
• 英文别名: tert-butyl (2S,4R,5R)-1-(4-tert-butyl-3-methoxybenzoyl)-4-(hydroxymethyl)-2-(2-methylpropyl)-5-(1,3-thiazol-2-yl)pyrrolidine-2-carboxylate
• 化学式: C₂₉H₄₂N₂O₅S
• 分子量: 530.729
• InChiKey: WHEBBORIKZDPFZ-MMOLPGFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  rac-(2S,4R,5R)-2-isobutyl-1-(3-methoxy-4-tert-butylbenzoyl)-4-hydroxymethyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid 2-tert-butyl ester 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 (2S,4R,5R)-2-isobutyl-1-(3-methoxy-4-tert-butylbenzoyl)-4-ethoxymethyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Optimization of Novel Acyl Pyrrolidine Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase Leading to a Development Candidate

  摘要：

  Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties.

  DOI：

  10.1021/jm061207r
• 作为产物：
  描述：

  2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid tert-butyl ester 在 锂硼氢 、 (R)-1,1'-binaphthyl-2,2'-phosphoric acid 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 35.0h， 生成 rac-(2S,4R,5R)-2-isobutyl-1-(3-methoxy-4-tert-butylbenzoyl)-4-hydroxymethyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid 2-tert-butyl ester
  参考文献：
  名称：

  Optimization of Novel Acyl Pyrrolidine Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase Leading to a Development Candidate

  摘要：

  Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties.

  DOI：

  10.1021/jm061207r

文献信息

• [EN] 1-ACYL-PYRROLIDINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS<br/>[FR] DERIVES DE 1-ACYL-PYRROLIDINE DESTINES AU TRAITEMENT D'INFECTIONS VIRALES
  申请人：GLAXO GROUP LTD

  公开号：WO2004037818A1

  公开（公告）日：2004-05-06

  Anti-viral agents of Formula (I) wherein: A represents hydroxy; D represents aryl or heteroaryl; E represents hydrogen, C1-6alkyl, aryl, heteroaryl or heterocyclyl; G represents hydrogen or optionally substituted C1-6alkyl; J represents C1-6alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl;and salts, solvates and esters thereof; provided that when A is esterified to form -OR where R is selected from straight or branched chain alkyl, aralkyl, aryloxyalkyl, or aryl, then R is other than tert-butyl;processes for their preparation, pharmaceutical compositions comprising them, and methods of using them in HCV treatment are provided.

  化学式（I）的抗病毒剂其中：A代表羟基；D代表芳基或杂芳基；E代表氢、C1-6烷基、芳基、杂芳基或杂环烷基；G代表氢或可选择地取代的C1-6烷基；J代表C1-6烷基、杂环烷基烷基、芳基烷基或杂芳基烷基；及其盐、溶剂合物和酯；提供它们的制备方法、包含它们的药物组合物以及在丙型肝炎病毒治疗中使用它们的方法。
• US7304087B2
  申请人：——

  公开号：US7304087B2

  公开（公告）日：2007-12-04
• Optimization of Novel Acyl Pyrrolidine Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase Leading to a Development Candidate
  作者：Martin J. Slater、Elizabeth M. Amphlett、David M. Andrews、Gianpaolo Bravi、George Burton、Anne G. Cheasty、John A. Corfield、Malcolm R. Ellis、Rebecca H. Fenwick、Stephanie Fernandes、Rossella Guidetti、David Haigh、C. David Hartley、Peter D. Howes、Deborah L. Jackson、Richard L. Jarvest、Victoria L. H. Lovegrove、Katrina J. Medhurst、Nigel R. Parry、Helen Price、Pritom Shah、Onkar M. P. Singh、Richard Stocker、Pia Thommes、Claire Wilkinson、Alan Wonacott

  DOI：10.1021/jm061207r

  日期：2007.3.1

  Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties.