(2S,4S,5R)-4-(aminocarbonyl)-1-(3-bromo-4-tert-butylbenzoyl)-2-isobutyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid tert-butyl ester | 927436-29-1

• 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: (2S,4S,5R)-4-(aminocarbonyl)-1-(3-bromo-4-tert-butylbenzoyl)-2-isobutyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid tert-butyl ester
• 英文别名: rel-(2S,4S,5R)-4-(aminocarbonyl)-1-(3-bromo4-tert-butylbenzoyl)-2-isobutyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid tert-butyl ester；tert-butyl (2S,4S,5R)-1-(3-bromo-4-tert-butylbenzoyl)-4-carbamoyl-2-(2-methylpropyl)-5-(1,3-thiazol-2-yl)pyrrolidine-2-carboxylate
• CAS: 927436-29-1
• 化学式: C₂₈H₃₈BrN₃O₄S
• 分子量: 592.597
• InChiKey: AXWIRBUJFZNSMP-LVFJRYOWSA-N

物化性质

• 沸点：
  692.9±55.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4S,5R)-4-(aminocarbonyl)-1-(3-bromo-4-tert-butylbenzoyl)-2-isobutyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 16.0h， 以66%的产率得到(2S,4S,5R)-1-(3-bromo-4-tert-butyl-benzoyl)-4-carbamoyl-2-isobutyl-5-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 (-)-di-O,O'-p-tolyl-L-tartaric acid 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 (2S,4S,5R)-4-(aminocarbonyl)-1-(3-bromo-4-tert-butylbenzoyl)-2-isobutyl-5-(1,3-thiazol-2-yl)-pyrrolidine-2-carboxylic acid 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

• 4-(5-Membered)-heteroaryl acyl pyrrolidine derivatives as hcv inhibitors
  申请人：Bravi Gianpalol

  公开号：US20050043545A1

  公开（公告）日：2005-02-24

  Novel anti-viral agents of Formula wherein: A represents OR 1 , NR 1 R 2 , or R 1 wherein R 1 and R 2 are hydrogen, C 1-6 alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; or R 1 and R 2 together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; B represents C(O)R 3 wherein R 3 is C 1-6 alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; C represents C 1-6 alkyl, aryl, heteroaryl or heterocyclyl; D represents a saturated or unsaturated optionally substituted 5-membered heterocyclic ring; E represents hydrogen or C 1-6 alkyl; F represents hydrogen, C 1-6 alkyl, aryl or heteroaryl; and G represents hydrogen, C 1-6 alkyl, heterocyclylalkyl, arylalkyl or heteroarylalkyl; and salts and solvates thereof, processes for their preparation and methods of using them in HCV treatment are provided.

  本发明提供了Formula中的新型抗病毒剂，其中：A代表OR1，NR1R2或R1，其中R1和R2为氢，C1-6烷基，芳基，杂芳基，芳基烷基或杂芳基烷基；或者R1和R2与它们连接的氮原子共同形成一个5或6成员饱和环；B代表C（O）R3，其中R3为C1-6烷基，芳基，杂芳基，芳基烷基或杂芳基烷基；C代表C1-6烷基，芳基，杂芳基或杂环基；D代表饱和或不饱和的可选取代的5成员杂环环；E代表氢或C1-6烷基；F代表氢，C1-6烷基，芳基或杂芳基；G代表氢，C1-6烷基，杂环基烷基，芳基烷基或杂芳基烷基；以及其盐和溶剂化物，提供了其制备方法和在HCV治疗中使用的方法。
• 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.