{(S)-1-[((S)-1-Isobutylcarbamoyl-propylamino)-methyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester | 827579-59-9

• 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: {(S)-1-[((S)-1-Isobutylcarbamoyl-propylamino)-methyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]carbamate
• CAS: 827579-59-9
• 化学式: C₂₂H₃₇N₃O₃
• 分子量: 391.554
• InChiKey: IZOOGPZVASUUKA-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {(S)-1-[((S)-1-Isobutylcarbamoyl-propylamino)-methyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 (S)-2-((S)-2-Amino-3-phenyl-propylamino)-N-isobutyl-butyramide; compound with GENERIC INORGANIC NEUTRAL COMPONENT
  参考文献：
  名称：

  BACE-1 inhibition by a series of ψ[CH2NH] reduced amide isosteres

  摘要：

  A series of beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a psi(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay.

  DOI：

  10.1016/j.bmcl.2006.04.076
• 作为产物：
  描述：

  (S)-tert-butyl [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 {(S)-1-[((S)-1-Isobutylcarbamoyl-propylamino)-methyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibitors of Memapsin 2 Cleavage for the Treatment of Alzheimer's Disease

  摘要：

  蛋白酶如膜蛋白酶2是重要的酶，发挥着在各种疾病中的作用，包括阿尔茨海默病。发明者已经开发了膜蛋白酶2的抑制剂以及在治疗疾病中使用的方法。

  公开号：

  US20140066488A1

文献信息

• 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.