(2S,3S)-2,3-diacetyloxy-4-[2,2-dimethoxyethyl-[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid | 1219696-68-0

• 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: (2S,3S)-2,3-diacetyloxy-4-[2,2-dimethoxyethyl-[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
• CAS: 1219696-68-0
• 化学式: C₁₉H₃₁NO₁₁
• 分子量: 449.455
• InChiKey: QPBAZUZMGRCOMZ-BPUTZDHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2,3-diacetyloxy-4-[2,2-dimethoxyethyl-[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid 在 氯化亚砜 、 硫酸 、 silica gel 作用下， 以 甲苯 为溶剂， 生成 (2S)-2-[(5S,7S)-7-(4-phenylethylpiperazine-1-carbonyl)-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]oct-3-yl]-4-methylpentanoic acid methyl ester
  参考文献：
  名称：

  Identification of Inhibitors of Drug-Resistant Candida albicans Strains from a Library of Bicyclic Peptidomimetic Compounds

  摘要：

  The screening of a library of small molecule peptidomimetics toward secreted aspartic proteinase-2 (SAP2) of Candida aibicans allowed us to identify two compounds that showed in vitro inhibitory potency comparable to pepstatin A. In an experimental model of vaginal candidiasis, the two candidate compounds were as active as a therapeutic dose of fluconazole. Importantly, this activity was fully preserved when the challenger was a fluconazole-resistant strain of the fungus. Altogether, our data demonstrate SAP2 as a valid C. albicans target for the development of new drugs against this important human pathogen.

  DOI：

  10.1021/jm901734u
• 作为产物：
  描述：

  L-亮氨酸甲酯盐酸盐 在 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (2S,3S)-2,3-diacetyloxy-4-[2,2-dimethoxyethyl-[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  Identification of Inhibitors of Drug-Resistant Candida albicans Strains from a Library of Bicyclic Peptidomimetic Compounds

  摘要：

  The screening of a library of small molecule peptidomimetics toward secreted aspartic proteinase-2 (SAP2) of Candida aibicans allowed us to identify two compounds that showed in vitro inhibitory potency comparable to pepstatin A. In an experimental model of vaginal candidiasis, the two candidate compounds were as active as a therapeutic dose of fluconazole. Importantly, this activity was fully preserved when the challenger was a fluconazole-resistant strain of the fungus. Altogether, our data demonstrate SAP2 as a valid C. albicans target for the development of new drugs against this important human pathogen.

  DOI：

  10.1021/jm901734u

文献信息

• Bicyclic peptidomimetic inhibitors of aspartyl-proteases for the treatment of infectious diseases
  申请人：Universita' Degli Studi di Firenze

  公开号：EP2189462B9

  公开（公告）日：2012-06-13
• Bicyclic peptidomimetics targeting secreted aspartic protease 2 (SAP2) from Candida albicans reveal a constrained inhibitory chemotype
  作者：Chiara Calugi、Andrea Trabocchi、Flavia De Bernardis、Silvia Arancia、Pierluigi Navarra、Roberto Cauda、Antonio Cassone、Antonio Guarna

  DOI：10.1016/j.bmc.2012.09.031

  日期：2012.12

  The in vitro screening of stereoisomeric bicyclic peptidomimetics towards SAP2 of Candida albicans revealed a constrained chemotype as aspartic protease inhibitor in the micromolar to nanomolar range. The results indicated that the acetal bridge may serve as a transition-state isostere, and that the right match between interactions with subsites and the orientation by hydrogen bonding with Gly85 is the main requisite for inhibitory activity. Molecular docking calculations suggested the bicyclic acetal scaffold to be capable of interacting with the two catalytic aspartic acids, thus resulting in good inhibitory activity with only two hydrophobic groups addressing the enzyme catalytic subsites. (C) 2012 Elsevier Ltd. All rights reserved.