(S)-1-[(R)-2-Hydroxy-2-((9S,12S)-9-isopropyl-7,10-dioxo-2-oxa-8,11-diaza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-ethyl]-piperidine-2-carboxylic acid tert-butylamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (S)-1-[(R)-2-Hydroxy-2-((9S,12S)-9-isopropyl-7,10-dioxo-2-oxa-8,11-diaza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-ethyl]-piperidine-2-carboxylic acid tert-butylamide
• 英文别名: (2S)-N-tert-butyl-1-[(2R)-2-hydroxy-2-[(3S,6S)-6-isopropyl-5,8-dioxo-13-oxa-4,7-diazabicyclo[12.2.2]octadeca-1(16),14,17-trien-3-yl]ethyl]piperidine-2-carboxamide；(2S)-N-tert-butyl-1-[(2R)-2-[(9S,12S)-7,10-dioxo-9-propan-2-yl-2-oxa-8,11-diazabicyclo[12.2.2]octadeca-1(16),14,17-trien-12-yl]-2-hydroxyethyl]piperidine-2-carboxamide
• 化学式: C₃₀H₄₈N₄O₅
• 分子量: 544.735
• InChiKey: UKHWRIRAODZHTP-CLPFNFTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-{4-[(S)-2-((S)-2-Amino-3-methyl-butyrylamino)-4-((S)-2-tert-butylcarbamoyl-piperidin-1-yl)-3-hydroxy-butyl]-phenoxy}-pentanoic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 (S)-1-[(R)-2-Hydroxy-2-((9S,12S)-9-isopropyl-7,10-dioxo-2-oxa-8,11-diaza-bicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)-ethyl]-piperidine-2-carboxylic acid tert-butylamide
  参考文献：
  名称：

  Structure-activity relationships for macrocyclic peptidomimetic inhibitors of HIV-1 protease

  摘要：

  A rational approach to developing inhibitors of proteolytic enzymes is the systematic modification of their peptide substrates to proteolytically stable, low molecular weight, nonpeptidic inhibitors. Replacing the scissile amide bond with a noncleavable transition state isostere usually gives potent protease inhibitors, but the remaining hydrolysable amide bonds render the inhibitors unstable to peptidases generally. Attempts to replace them with retention of inhibitor potency has proved difficult(1,2) due to the unpredictable cooperative influences of such variations on the conformations of both neighbouring inhibitor groups and enzyme residues. We recently described a method(3) for regioselectively fixing the conformation of inhibitor components and now show effects on activity of varying both the 'free' and 'fixed' components.

  DOI：

  10.1016/0960-894x(96)00468-4

文献信息

• Structure-activity relationships for macrocyclic peptidomimetic inhibitors of HIV-1 protease
  作者：G. Abbenante、D.A. Bergman、R.I. Brinkworth、D.R. March、R.C. Reid、P.A. Hunt、I.W. James、R.J. Dancer、B. Garnham、M.L. Stoermer、D.P. Fairlie

  DOI：10.1016/0960-894x(96)00468-4

  日期：1996.11

  A rational approach to developing inhibitors of proteolytic enzymes is the systematic modification of their peptide substrates to proteolytically stable, low molecular weight, nonpeptidic inhibitors. Replacing the scissile amide bond with a noncleavable transition state isostere usually gives potent protease inhibitors, but the remaining hydrolysable amide bonds render the inhibitors unstable to peptidases generally. Attempts to replace them with retention of inhibitor potency has proved difficult(1,2) due to the unpredictable cooperative influences of such variations on the conformations of both neighbouring inhibitor groups and enzyme residues. We recently described a method(3) for regioselectively fixing the conformation of inhibitor components and now show effects on activity of varying both the 'free' and 'fixed' components.