methyl (2S)-4-methyl-2-[(1R,5R,7R)-2-oxo-7-(piperidine-1-carbonyl)-6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl]pentanoate | 1415027-17-6

• 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: methyl (2S)-4-methyl-2-[(1R,5R,7R)-2-oxo-7-(piperidine-1-carbonyl)-6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl]pentanoate
• CAS: 1415027-17-6
• 化学式: C₁₈H₂₈N₂O₆
• 分子量: 368.43
• InChiKey: MNTZQPYJSPFTGX-GBJTYRQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S)-4-methyl-2-[(1R,5R,7R)-2-oxo-7-(piperidine-1-carbonyl)-6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl]pentanoate 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 (S)-N-butyl-4-methyl-2-((1R,5R,7R)-2-oxo-7-(piperidine-1-carbonyl)-6,8-dioxa-3-dioxa-3-azabicyclo[3.2.1]octan-3-yl)pentanamide
  参考文献：
  名称：

  Identification of constrained peptidomimetic chemotypes as HIV protease inhibitors

  摘要：

  Small-molecule peptidomimetic inhibitors that already showed activity towards Secreted aspartic protease 2 as anti-Candida agents are herein presented as candidate HIV protease inhibitors. A library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was screened towards HIV protease, resulting in the identification of hit compounds possessing IC50 in the sub-micromolar range, and showing the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.

  DOI：

  10.1016/j.ejmech.2014.07.049
• 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 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 37.25h， 生成 methyl (2S)-4-methyl-2-[(1R,5R,7R)-2-oxo-7-(piperidine-1-carbonyl)-6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl]pentanoate
  参考文献：
  名称：

  Bicyclic peptidomimetics targeting secreted aspartic protease 2 (SAP2) from Candida albicans reveal a constrained inhibitory chemotype

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2012.09.031

文献信息

• Identification of constrained peptidomimetic chemotypes as HIV protease inhibitors
  作者：Chiara Calugi、Antonio Guarna、Andrea Trabocchi

  DOI：10.1016/j.ejmech.2014.07.049

  日期：2014.9

  Small-molecule peptidomimetic inhibitors that already showed activity towards Secreted aspartic protease 2 as anti-Candida agents are herein presented as candidate HIV protease inhibitors. A library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was screened towards HIV protease, resulting in the identification of hit compounds possessing IC50 in the sub-micromolar range, and showing the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.
• 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.