tert-butyl [(2S,3R)-3-hydroxy-1-(isobutylamino)-1-oxobutan-2-yl]carbamate | 1228072-81-8

• 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 [(2S,3R)-3-hydroxy-1-(isobutylamino)-1-oxobutan-2-yl]carbamate
• 英文别名: tert-butyl N-[(2S,3R)-3-hydroxy-1-(2-methylpropylamino)-1-oxobutan-2-yl]carbamate
• CAS: 1228072-81-8
• 化学式: C₁₃H₂₆N₂O₄
• 分子量: 274.36
• InChiKey: IZHPAWGTEAHENX-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [(2S,3R)-3-hydroxy-1-(isobutylamino)-1-oxobutan-2-yl]carbamate 在 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 17.5h， 生成 tert-butyl N-[(2S)-1-[[(2S,3R)-3-hydroxy-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure

  摘要：

  The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S-1' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K-i = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases.

  DOI：

  10.1021/jm3008823
• 作为产物：
  描述：

  Boc-L-苏氨酸 、 异丁胺 在 1-羟基苯并三唑一水物 、 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 二氯甲烷 为溶剂， 反应 17.0h， 以91%的产率得到tert-butyl [(2S,3R)-3-hydroxy-1-(isobutylamino)-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure

  摘要：

  The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S-1' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K-i = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases.

  DOI：

  10.1021/jm3008823

文献信息

• [EN] INHIBITORS OF BACE 1 AND METHODS FOR TREATING ALZHEIMER'S DISEASE<br/>[FR] INHIBITEURS DE BACE 1 ET MÉTHODES DE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2010065861A3

  公开（公告）日：2010-08-19
• US8859590B2
  申请人：——

  公开号：US8859590B2

  公开（公告）日：2014-10-14
• Structure-Based Design of Highly Selective β-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein–Ligand X-ray Crystal Structure
  作者：Arun K. Ghosh、Kalapala Venkateswara Rao、Navnath D. Yadav、David D. Anderson、Navnath Gavande、Xiangping Huang、Simon Terzyan、Jordan Tang

  DOI：10.1021/jm3008823

  日期：2012.11.8

  The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S-1' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K-i = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases.