2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid tert-butyl ester | 521955-41-9

• 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: 2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid tert-butyl ester
• 英文别名: 2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methyl-pentanoic acid tert-butyl ester；2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid, tert-butyl ester；tert-butyl 4-methyl-2-(1,3-thiazol-2-ylmethylideneamino)pentanoate
• CAS: 521955-41-9
• 化学式: C₁₄H₂₂N₂O₂S
• 分子量: 282.407
• InChiKey: ODOGUYJIAWRTIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  355.8±44.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  79.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid tert-butyl ester 在 lithium aluminium tetrahydride 、 (R)-1,1'-binaphthyl-2,2'-phosphoric acid 、 sodium hydride 、 三乙胺 、 三氟乙酸 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 66.33h， 生成 (4S,5R)-1-{[4-(1,1-dimethylethyl)-3-(methoxy)phenyl]carbonyl}-4-(hydroxymethyl)-2-(2-methylpropyl)-5-(1,3-thiazol-2-yl)-L-proline
  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-醛基噻唑 在 三乙胺 、 leucine t-butyl ester hydrochloride 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 2-[N-(1,3-thiazol-2-ylmethylene)amino]-4-methylpentanoic acid tert-butyl ester
  参考文献：
  名称：

  [EN] 1-CARBONYL-4-CYANO-PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES AS HEPATITIS C VIRUS INHIBITORS
  [FR] COMPOSES

  摘要：

  公开号：

  WO2004009543A3

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。
• [EN] ACYL DIHYDRO PYRROLE DERIVATIVES AS HCV INHIBITORS<br/>[FR] DERIVES ACYL-DIHYDRO-PYRROLE UTILISES EN TANT QU'INHIBITEURS DU VHC
  申请人：GLAXO GROUP LTD

  公开号：WO2005103045A1

  公开（公告）日：2005-11-03

  Novel anti-viral agents of Formula (I) in which: A represents hydroxy; D represents aryl or heteroaryl; E represents hydrogen, C1-6alkyl, aryl, heteroaryl or heterocyclyl; G represents hydrogen or C1-6alkyl optionally substituted by one or more substituents selected from halo, OR1, SR1, C(O)NR2R3, CO2H, C(O)R4, CO2R4, NR2R3, NHC(O)R4, NHCO2R4, NHC(O)NR5R6, SO2NR5R6, SO2R4, nitro, cyano, aryl, heteroaryl and heterocyclyl; R1 represents hydrogen, C1-6alkyl, arylalkyl, or heteroarylalkyl; R2 and R3 are independently selected from hydrogen, C1-6alkyl, aryl and heteroaryl; or R2 and R3 together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; R4 is selected from the group consisting of C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; R5 and R6 are independently selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; or R5 and R6 together with the nitrogen atom to which they are attached form a 5 or 6 membered saturated cyclic group; and 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.

  公式（I）中的新型抗病毒剂：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C1-6烷基，可选择地被来自卤素、OR1、SR1、C(O)NR2R3、CO2H、C(O)R4、CO2R4、NR2R3、NHC(O)R4、NHCO2R4、NHC(O)NR5R6、SO2NR5R6、SO2R4、硝基、氰基、芳基、杂芳基和杂环烷基的一个或多个取代基取代；R1代表氢、C1-6烷基、芳基烷基或杂芳基烷基；R2和R3独立地选自氢、C1-6烷基、芳基和杂芳基；或R2和R3与它们连接的氮原子一起形成5或6个成员饱和环；R4从由C1-6烷基、芳基、杂芳基、芳基烷基和杂芳基烷基组成的群体中选择；R5和R6独立地选自氢、C1-6烷基、芳基、杂芳基、芳基烷基和杂芳基烷基的群体；或R5和R6与它们连接的氮原子一起形成5或6个成员饱和环；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；但是当A酯化形成-OR（其中R从直链或支链烷基、芳基烷基、芳基氧烷基或芳基中选择）时，则R不是叔丁基；提供了它们的制备方法、包括它们的药物组合物以及在HCV治疗中使用它们的方法。
• [EN] 1- (HETERO)AROYL-PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES USEFUL AS ANTI.VIRAL AGENTS<br/>[FR] DERIVES D'ACIDE 1- (HETERO)AROYL-PYRROLIDINE-2-CARBOXYLIQUE UTILES COMME AGENTS ANTI-VIRAUX
  申请人：GLAXO GROUP LTD

  公开号：WO2004076415A1

  公开（公告）日：2004-09-10

  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 SOnRa; n is 1 or 2; Ra represents optionally substituted C1-6alkyl or aryl; 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 and methods of using them in HCV treatment are provided.

  Formula (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SOnRa；n为1或2；Ra代表可选择取代的C1-6烷基或芳基；J代表C1-6烷基、杂环烷基烷基、芳基烷基或杂芳基烷基；以及它们的盐、溶剂合物和酯；但是当A酯化形成-OR，其中R选自直链或支链烷基、芳基、芳氧基烷基或芳基时，则R不是叔丁基；提供了它们的制备方法以及在HCV治疗中使用它们的方法。
• [EN] 5-THIAZOLE SUBSTITUTED 2-PYRROLIDINE-CARBOXYLIC ACIDS<br/>[FR] ACIDES 2-PYRROLIDINE-CARBOXYLIQUES A SUBSTITUTION 5-THIAZOLE
  申请人：GLAXO GROUP LTD

  公开号：WO2004060889A1

  公开（公告）日：2004-07-22

  Anti-viral agents of Formula (1a) wherein: RA represents hydroxy; RB represents 4-tert-butylbenzoyl further substituted in the meta-position by halo or C1-3alkoxy; RC represents 2-thiazolyl, 5-methylthiazol-2-yl, or 4-thiazolyl; RD represents methyl; X represents isobutyl; and salts, solvates and esters thereof; provided that when RA is esterified to form -OR where R is selected from straight or branched chain alkyl, arakyl, aryloxyalkyl, or aryl, then R is other than tert-butyl; processes for their preparation and their use in HCV treatment are provided.

  化学式（1a）的抗病毒药剂，其中：RA代表羟基；RB代表4-叔丁基苯甲酰基，进一步在间位被卤素或C1-3烷氧基取代；RC代表2-噻唑基，5-甲基噻唑-2-基，或4-噻唑基；RD代表甲基；X代表异丁基；以及它们的盐、溶剂合物和酯；前提是当RA酯化形成-OR，其中R选自直链或支链烷基、芳基、芳氧基烷基或芳基时，R不是叔丁基；提供了它们的制备方法以及在HCV治疗中的应用。
• Acyl dihydro pyrrole derivatives as hcv inhibitors
  申请人：Bravi Gianpaolo

  公开号：US20050009873A1

  公开（公告）日：2005-01-13

  Novel anti-viral agents of Formula (I) 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; D represents C 1-6 alkyl, aryl, heteroaryl or heterocyclyl; E 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; 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.

  公式（I）的新型抗病毒药物，其中：A代表OR1，NR1R2或R1，其中R1和R2是氢，C1-6烷基，芳基，杂芳基，芳基烷基或杂芳基烷基；或R1和R2与它们附着的氮原子一起形成一个5或6成员饱和环；B代表C（O）R3，其中R3是C1-6烷基，芳基，杂芳基，芳基烷基或杂芳基烷基；D代表C1-6烷基，芳基，杂芳基或杂环基；E代表OR1，NR1R2或R1，其中R1和R2是氢，C1-6烷基，芳基，杂芳基，芳基烷基或杂芳基烷基；或R1和R2与它们附着的氮原子一起形成一个5或6成员饱和环；F代表氢，C1-6烷基，芳基或杂芳基；G代表氢，C1-6烷基，杂环烷基，芳基烷基或杂芳基烷基；以及它们的盐和溶剂合物，提供了其制备过程以及在HCV治疗中使用它们的方法。