(R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester | 393568-96-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2R)-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate
• CAS: 393568-96-2
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: SLSOSKGFUOFMCP-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 、 甲基三苯基溴化膦 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 (R)-N-(tert-butoxycarbonyl)-3-amino-4-(p-benzyloxyphenyl)-1-butene
  参考文献：
  名称：

  Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase

  摘要：

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.

  DOI：

  10.1021/jm101227t
• 作为产物：
  描述：

  Boc-D-Tyr(Bzl)-OH 在 N-甲基吗啉 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.58h， 生成 (R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase

  摘要：

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.

  DOI：

  10.1021/jm101227t

文献信息

• Compounds and inhibitors of phospholipases
  申请人：——

  公开号：US20040033995A1

  公开（公告）日：2004-02-19

  The present invention relates generally to amino acid derivatives and to methods of making the same. In particular, the invention relates to compounds bearing a stereochemical identity, that is, the same stereochemistry, with the chiral &agr;-carbon of D-&agr;-amino acids and their use in methods of therapy, including the treatment of inflammatory diseases, and to compositions and enantiomeric mixtures containing them.

  本发明一般涉及氨基酸衍生物及其制备方法。具体而言，该发明涉及具有立体化学特性的化合物，即与D-α-氨基酸的手性α-碳具有相同立体化学的化合物，以及它们在治疗方法中的应用，包括治疗炎症性疾病，以及含有它们的组合物和对映体混合物。
• [EN] COMPOUNDS AND INHIBITORS OF PHOSPHOLIPASES<br/>[FR] COMPOSES ET INHIBITEURS DE PHOSPHOLIPASES
  申请人：UNIV QUEENSLAND

  公开号：WO2002008189A1

  公开（公告）日：2002-01-31

  The present invention relates generally to amino acid derivatives and to methods of making the same. In particular, the invention relates to compounds bearing a stereochemical identity, that is, the same stereochemistry, with the chiral α-carbon of D-α-amino acids and their use in methods of therapy, including the treatment of inflammatory diseases, and to compositions and enantiomeric mixtures containing them.

  本发明通常涉及氨基酸衍生物及其制备方法。特别地，本发明涉及具有立体化学同一性的化合物，即具有D-α-氨基酸的手性α-碳的同一立体化学，以及它们在治疗方法中的使用，包括治疗炎症性疾病，以及含有它们的组合物和对映体混合物。
• COMPOUNDS AND INHIBITORS OF PHOSPHOLIPASES
  申请人：THE UNIVERSITY OF QUEENSLAND

  公开号：EP1309552A1

  公开（公告）日：2003-05-14
• EP1309552A4
  申请人：——

  公开号：EP1309552A4

  公开（公告）日：2005-07-20
• US7253194B2
  申请人：——

  公开号：US7253194B2

  公开（公告）日：2007-08-07