4-{[(Benzyloxy)carbonyl]amino}thiane-4-carboxylic acid | 39974-69-1

• 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: 4-{[(Benzyloxy)carbonyl]amino}thiane-4-carboxylic acid
• 英文别名: 4-(phenylmethoxycarbonylamino)thiane-4-carboxylic acid
• CAS: 39974-69-1
• 化学式: C₁₄H₁₇NO₄S
• 分子量: 295.359
• InChiKey: LEBCWZAQFFYVQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-amino-1-chloro-5-phenylpentan-2-one hydrochloride 、 4-{[(Benzyloxy)carbonyl]amino}thiane-4-carboxylic acid 在 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 二氯甲烷 为溶剂， 反应 12.0h， 生成 benzyl (S)-(4-((1-chloro-2-oxo-5-phenylpentan-3-yl)carbamoyl)tetrahydro-2H-thiopyran-4-yl)carbamate
  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
• 作为产物：
  描述：

  苯甲氧羰酰琥珀酰亚胺 、 4-氨基四氢噻喃-4-甲酸 在 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 以72%的产率得到4-{[(Benzyloxy)carbonyl]amino}thiane-4-carboxylic acid
  参考文献：
  名称：

  通过四氢噻喃类似物的脱硫形成的扩展的二乙基甘氨酸同肽

  摘要：

  二乙基甘氨酸（Deg）同系肽采用罕见的2.0 5螺旋构象，即给定序列的肽可以采用的最长的三维结构。尽管具有这种独特的构象特征，但由于其反应性差，Deg很少用于肽设计中。在本文中，我们显示了由反应性更高的含四氢噻喃的前体形成的低聚物的还原脱硫提供了构建迄今最长的Deg同系肽的实用方法，并且我们详细介绍了Deg低聚物及其杂环前体的构象研究。

  DOI：

  10.1021/acs.orglett.9b00501

文献信息

• Extended Diethylglycine Homopeptides Formed by Desulfurization of Their Tetrahydrothiopyran Analogues
  作者：Marta De Zotti、Jonathan Clayden

  DOI：10.1021/acs.orglett.9b00501

  日期：2019.4.5

  Diethylglycine (Deg) homopeptides adopt the rare 2.05-helical conformation, the longest three-dimensional structure that a peptide of a given sequence can adopt. Despite this unique conformational feature, Deg is rarely used in peptide design because of its poor reactivity. In this paper, we show that reductive desulfurization of oligomers formed from more reactive tetrahydrothiopyran-containing precursors

  二乙基甘氨酸（Deg）同系肽采用罕见的2.0 5螺旋构象，即给定序列的肽可以采用的最长的三维结构。尽管具有这种独特的构象特征，但由于其反应性差，Deg很少用于肽设计中。在本文中，我们显示了由反应性更高的含四氢噻喃的前体形成的低聚物的还原脱硫提供了构建迄今最长的Deg同系肽的实用方法，并且我们详细介绍了Deg低聚物及其杂环前体的构象研究。
• 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.