benzyl (2S)-2-[[(3S)-2-oxo-5-phenyl-1-(3-phenylpropylsulfanyl)pentan-3-yl]carbamoyl]pyrrolidine-1-carboxylate | 1569294-44-5

• 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: benzyl (2S)-2-[[(3S)-2-oxo-5-phenyl-1-(3-phenylpropylsulfanyl)pentan-3-yl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1569294-44-5
• 化学式: C₃₃H₃₈N₂O₄S
• 分子量: 558.742
• InChiKey: QMEJSSCAGCTRRX-KYJUHHDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-3-(<(tert-butoxy)carbonyl>amino)-1-diazo-5-phenylpentan-2-one 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 26.0h， 生成 benzyl (2S)-2-[[(3S)-2-oxo-5-phenyl-1-(3-phenylpropylsulfanyl)pentan-3-yl]carbamoyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum

  摘要：

  A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based a-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80 nM against FP-2 and 60 nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.062

文献信息

• Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum
  作者：David J. Weldon、Falgun Shah、Amar G. Chittiboyina、Anjaneyulu Sheri、Raji Reddy Chada、Jiri Gut、Philip J. Rosenthal、Develeena Shivakumar、Woody Sherman、Prashant Desai、Jae-Chul Jung、Mitchell A. Avery

  DOI：10.1016/j.bmcl.2014.01.062

  日期：2014.3

  A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based a-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80 nM against FP-2 and 60 nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria. (c) 2014 Elsevier Ltd. All rights reserved.