{(S)-1-[(S)-1-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-{(S)-2-methyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-propylcarbamoyl}-pentylcarbamoyl)-ethylcarbamoyl]-3,3-difluoro-propyl}-carbamic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: {(S)-1-[(S)-1-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-{(S)-2-methyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-propylcarbamoyl}-pentylcarbamoyl)-ethylcarbamoyl]-3,3-difluoro-propyl}-carbamic acid tert-butyl ester
• 英文别名: {(S)-1-[(S)-1-((2S,4S)-1-Benzyl-2-hydroxy-4-{(R)-2-methyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-propylcarbamoyl}-pentylcarbamoyl)-ethylcarbamoyl]-3,3-difluoro-propyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-4,4-difluoro-1-[[(2S)-1-[[(2S,3S,5R)-3-hydroxy-5-methyl-6-[[(2S)-3-methyl-1-oxo-1-(pyridin-4-ylmethylamino)butan-2-yl]amino]-6-oxo-1-phenylhexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxobutan-2-yl]carbamate
• 化学式: C₃₆H₅₂F₂N₆O₇
• 分子量: 718.842
• InChiKey: CLLUELOOOLMHGM-ZXSVIEFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  51
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  188
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (S)-2-N-叔丁氧羰基氨基-4,4-二氟丁酸 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 {(S)-1-[(S)-1-((1S,2S,4R)-1-Benzyl-2-hydroxy-4-{(S)-2-methyl-1-[(pyridin-4-ylmethyl)-carbamoyl]-propylcarbamoyl}-pentylcarbamoyl)-ethylcarbamoyl]-3,3-difluoro-propyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR

  摘要：

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.084

文献信息

• Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR
  作者：Jason Lamar、Jingdan Hu、Ana Belen Bueno、Hsiu-Chiung Yang、Deqi Guo、James D. Copp、James McGee、Bruce Gitter、David Timm、Patrick May、James McCarthy、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.084

  日期：2004.1

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.