benzyl (S)-1-((S)-1-(isobutylamino)-1-oxopropan-2-ylamino)-4-methylpentan-2-ylcarbamate | 1314806-99-9

• 英文名称: benzyl (S)-1-((S)-1-(isobutylamino)-1-oxopropan-2-ylamino)-4-methylpentan-2-ylcarbamate
• CAS: 1314806-99-9
• 化学式: C₂₁H₃₅N₃O₃
• 分子量: 377.527
• InChiKey: RVPVTCPVRLUPEI-HKUYNNGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  27.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  79.46
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  benzyl (S)-1-((S)-1-(isobutylamino)-1-oxopropan-2-ylamino)-4-methylpentan-2-ylcarbamate 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 三氟甲磺酸酐 、 palladium 10% on activated carbon 、 氢气 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 138.0h， 生成
  参考文献：
  名称：

  Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer’s BACE1 inhibitors

  摘要：

  In the course of a beta-site APP-cleaving enzyme 1 (BACE1) inhibitor discovery project an in situ synthesis/screening protocol was employed to prepare 120 triazole-linked reduced amide isostere inhibitors. Among these compounds, four showed modest (single digit micromolar) BACE1 inhibition. Our ligand design was based on a potent reduced amide isostere 1, wherein the P(2) amide moiety was replaced with an anti-1,2,3-triazole unit. Unfortunately, this replacement resulted in a 1000-fold decrease in potency. Docking studies of triazole-linked reduced amide isostere A3Z10 and potent oxadiazole-linked tertiary carbinamine 2a with BACE1 suggests that the docking poses of A3Z10 and 2a in the active sites are quite similar, with one exception. In the docked structures the placement of the protonated amine that engages D228 differs considerably between 2a and A3Z10. This difference could account for the lower BACE1 inhibition potency of A3Z10 and related compounds relative to 2a. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.007
• 作为产物：
  描述：

  L-alanine isobutylamide 在 三乙酰氧基硼氢化钠 、 magnesium sulfate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.08h， 生成 benzyl (S)-1-((S)-1-(isobutylamino)-1-oxopropan-2-ylamino)-4-methylpentan-2-ylcarbamate
  参考文献：
  名称：

  Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer’s BACE1 inhibitors

  摘要：

  In the course of a beta-site APP-cleaving enzyme 1 (BACE1) inhibitor discovery project an in situ synthesis/screening protocol was employed to prepare 120 triazole-linked reduced amide isostere inhibitors. Among these compounds, four showed modest (single digit micromolar) BACE1 inhibition. Our ligand design was based on a potent reduced amide isostere 1, wherein the P(2) amide moiety was replaced with an anti-1,2,3-triazole unit. Unfortunately, this replacement resulted in a 1000-fold decrease in potency. Docking studies of triazole-linked reduced amide isostere A3Z10 and potent oxadiazole-linked tertiary carbinamine 2a with BACE1 suggests that the docking poses of A3Z10 and 2a in the active sites are quite similar, with one exception. In the docked structures the placement of the protonated amine that engages D228 differs considerably between 2a and A3Z10. This difference could account for the lower BACE1 inhibition potency of A3Z10 and related compounds relative to 2a. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.007