tert-butyl [1S-(1'-cyclopropanecarbonyl-2'-oxo-hexahydro-(3'aS,6'aR)-spiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyrrole]-4'-carbonyl)-2-methyl-propyl]-carbamate | 484698-49-9

• 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: tert-butyl [1S-(1'-cyclopropanecarbonyl-2'-oxo-hexahydro-(3'aS,6'aR)-spiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyrrole]-4'-carbonyl)-2-methyl-propyl]-carbamate
• 英文别名: tert-butyl N-[(1S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxo-spiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-carbonyl]-2-methyl-propyl]carbamate；tert-butyl N-[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 484698-49-9
• 化学式: C₂₃H₃₅N₃O₅
• 分子量: 433.548
• InChiKey: YODDBSHHLFFXQX-ULQDDVLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl [1S-(1'-cyclopropanecarbonyl-2'-oxo-hexahydro-(3'aS,6'aR)-spiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyrrole]-4'-carbonyl)-2-methyl-propyl]-carbamate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 benzyl N-[(2S)-1-[(3aS,6aR)-4-(cyclopropanecarbonyl)-5-oxospiro[2,3,3a,6a-tetrahydropyrrolo[3,2-b]pyrrole-6,1'-cyclobutane]-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Pyrrolidine-5,5-trans-lactams. 2. The Use of X-ray Crystal Structure Data in the Optimization of P3 and P4 Substituents

  摘要：

  [GRAPHICS]In this, the second of two letters, we describe the elaboration of the pyrrolidine-5,5-trans-lactam template to delineate the requirements for optimal substitution of the pyrrolidine and lactam nitrogen atoms. Central to the strategy is the use of rapid iterative synthesis in conjunction with X-ray crystal structure determination of ligand-protein complexes.

  DOI：

  10.1021/ol027014p
• 作为产物：
  描述：

  tert-Butyl (3a'R,6a'S)-1'-(cyclopropanecarbonyl)-2'-oxohexahydro-4'H-spiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyrrole]-4'-carboxylate 在 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 二氯甲烷 、 乙腈 为溶剂， 生成 tert-butyl [1S-(1'-cyclopropanecarbonyl-2'-oxo-hexahydro-(3'aS,6'aR)-spiro[cyclobutane-1,3'-pyrrolo[3,2-b]pyrrole]-4'-carbonyl)-2-methyl-propyl]-carbamate
  参考文献：
  名称：

  Design and synthesis of spiro-cyclopentenyl and spiro--dithiolanyl substituted pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease

  摘要：

  Using the pyrrolidine-5,5-trans-lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 2b, with a spiro-cyclobutyl P1 substituent and an isopropyl carbonyl substituent at the lactam. nitrogen, has an IC50 value in the replicon cell-based assay of 3 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00274-9

文献信息

• Pyrrolidine-5,5-<i>trans</i>-lactams. 1. Synthesis and Incorporation into Inhibitors of Hepatitis C Virus NS3/4A Protease
  作者：David M. Andrews、Seb J. Carey、Helene Chaignot、Barry A. Coomber、Norman M. Gray、S. Lucy Hind、Paul S. Jones、Gail Mills、J. Ed Robinson、Martin J. Slater

  DOI：10.1021/ol027013x

  日期：2002.12.1

  [reaction: see text] In this, the first of two letters, we outline the use of the pyrrolidine-5,5-trans-lactam template to design small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. The hitherto unreported reaction of the acyl iminium ion precursor 4 with dialkyl-substituted silyl ketene acetals (e.g., 8b) is described. Compound 12b, with a spirocyclobutyl P1 substituent and

  [反应：参见正文]在此，我们以两个字母的第一个字母概述了吡咯烷5,5-反式内酰胺模板的用途，以设计小型，中性，基于机制的丙型肝炎NS3 / 4A蛋白酶抑制剂。描述了酰基亚胺离子前体4与二烷基取代的甲硅烷基烯酮缩醛（例如8b）的迄今未报道的反应。内酰胺氮上具有螺环丁基P1取代基和环丙基酰基取代基的化合物12b的ak（obs）/ I为400 M（-）（1）s（-）（1），并在基于复制子细胞的替代物中表现出活性HCV分析。
• Pyrrolidine-5,5-<i>trans</i>-lactams. 2. The Use of X-ray Crystal Structure Data in the Optimization of P3 and P4 Substituents
  作者：David M. Andrews、Helene Chaignot、Barry A. Coomber、Andrew C. Good、S. Lucy Hind、Martin R. Johnson、Paul S. Jones、Gail Mills、J. Ed Robinson、Tadeusz Skarzynski、Martin J. Slater、Donald O'N Somers

  DOI：10.1021/ol027014p

  日期：2002.12.1

  [GRAPHICS]In this, the second of two letters, we describe the elaboration of the pyrrolidine-5,5-trans-lactam template to delineate the requirements for optimal substitution of the pyrrolidine and lactam nitrogen atoms. Central to the strategy is the use of rapid iterative synthesis in conjunction with X-ray crystal structure determination of ligand-protein complexes.
• Design and synthesis of spiro-cyclopentenyl and spiro--dithiolanyl substituted pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease
  作者：David M. Andrews、Paul S. Jones、Gail Mills、S.Lucy Hind、Martin J. Slater、Naimisha Trivedi、Katrina J. Wareing

  DOI：10.1016/s0960-894x(03)00274-9

  日期：2003.5

  Using the pyrrolidine-5,5-trans-lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 2b, with a spiro-cyclobutyl P1 substituent and an isopropyl carbonyl substituent at the lactam. nitrogen, has an IC50 value in the replicon cell-based assay of 3 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.