(1S,5R,7S)-3-(1-methoxycarbonyl-3(S)-methylbutyl)-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylic acid methyl ester | 1219696-70-4

• 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: (1S,5R,7S)-3-(1-methoxycarbonyl-3(S)-methylbutyl)-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylic acid methyl ester
• 英文别名: methyl (1S,5R,7S)-3-[(2S)-1-methoxy-4-methyl-1-oxopentan-2-yl]-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylate
• CAS: 1219696-70-4
• 化学式: C₁₄H₂₁NO₇
• 分子量: 315.323
• InChiKey: HESLQXKJIOSWRT-VLEAKVRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-苯乙基哌嗪 、 (1S,5R,7S)-3-(1-methoxycarbonyl-3(S)-methylbutyl)-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylic acid methyl ester 以59%的产率得到(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：

  N-(2,2-dimethoxyethyl)-Leu-OMe 在 氯化亚砜 、 硫酸 、 silica gel 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (1S,5R,7S)-3-(1-methoxycarbonyl-3(S)-methylbutyl)-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylic 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

文献信息

• Identification of Inhibitors of Drug-Resistant <i>Candida albicans</i> Strains from a Library of Bicyclic Peptidomimetic Compounds
  作者：Andrea Trabocchi、Claudia Mannino、Fabrizio Machetti、Flavia De Bernardis、Silvia Arancia、Roberto Cauda、Antonio Cassone、Antonio Guarna

  DOI：10.1021/jm901734u

  日期：2010.3.25

  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.
• 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.