(3R)-8-cyclopropyl-6-[formyl(propane-2-sulfonyl)amino]-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester | 916314-84-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3R)-8-cyclopropyl-6-[formyl(propane-2-sulfonyl)amino]-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
• CAS: 916314-84-6
• 化学式: C₂₇H₂₈N₂O₆S₂
• 分子量: 540.661
• InChiKey: GGSCFHYQVIYUSN-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  102.75
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (3R)-8-cyclopropyl-6-[formyl(propane-2-sulfonyl)amino]-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones—Targeting virulence of uropathogenic E. coli

  摘要：

  Substituted bicyclic 2-pyridones, termed pilicides, are dipeptide mimetics that prevent pilus assembly in uropathogenic Escherichia coli. Here, we apply rational design to produce four classes of extended peptidomimetics based on two bioactive 2-pyridones. The key intermediate in the synthesis was an amino-functionalised 2-pyridone scaffold, which could be obtained via a mild and selective nitration and subsequent reduction. Procedures were then developed to further derivatize this amino-substituted core and a total of 24 extended peptidomimetics were synthesised and evaluated for chaperone affinity and in vivo antivirulence activity in P pili producing E coli. Enhanced affinities for the target protein were observed within the generated set of compounds, while the ability to prevent pilus assembly in vivo was significantly decreased compared to the parent lead compounds. The results suggest that the limited in vivo potencies of the analogues are either uptake/distribution related or due to loss in binding specificity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.017
• 作为产物：
  描述：

  methyl (3R)-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxo-2,3-dihydro-5H-[1,3 ]thiazolo[3,2-a]pyridine-3-carboxylate 在 N-(异丙基)氨基甲酸甲酯 、 potassium tert-butylate 、 氧气 、 乙酸酐 、 溶剂黄146 、 三氟乙酸 、 锌 、 sodium nitrite 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 (3R)-8-cyclopropyl-6-[formyl(propane-2-sulfonyl)amino]-7-(naphthalen-1-yl)methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones—Targeting virulence of uropathogenic E. coli

  摘要：

  Substituted bicyclic 2-pyridones, termed pilicides, are dipeptide mimetics that prevent pilus assembly in uropathogenic Escherichia coli. Here, we apply rational design to produce four classes of extended peptidomimetics based on two bioactive 2-pyridones. The key intermediate in the synthesis was an amino-functionalised 2-pyridone scaffold, which could be obtained via a mild and selective nitration and subsequent reduction. Procedures were then developed to further derivatize this amino-substituted core and a total of 24 extended peptidomimetics were synthesised and evaluated for chaperone affinity and in vivo antivirulence activity in P pili producing E coli. Enhanced affinities for the target protein were observed within the generated set of compounds, while the ability to prevent pilus assembly in vivo was significantly decreased compared to the parent lead compounds. The results suggest that the limited in vivo potencies of the analogues are either uptake/distribution related or due to loss in binding specificity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.017