benzyl (S)-1-((3S,7S,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-ylamino)-1-oxopropan-2-ylcarbamate

• 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: benzyl (S)-1-((3S,7S,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-ylamino)-1-oxopropan-2-ylcarbamate
• 英文别名: benzyl N-[(2S)-1-[[(2S,6S)-1-methyl-7-oxo-2-phenyl-5,6-dihydro-2H-azepin-6-yl]amino]-1-oxopropan-2-yl]carbamate
• 化学式: C₂₄H₂₇N₃O₄
• 分子量: 421.496
• InChiKey: XIQPUYCTBFZATM-YYWHXJBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苄氧羰基-L-丙氨酸 、 tert-butyl (3S,7S,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate 在 三氟乙酸 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以7.5%的产率得到benzyl (S)-1-((3S,7S,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-ylamino)-1-oxopropan-2-ylcarbamate
  参考文献：
  名称：

  Novel broad-spectrum inhibitors of bacterial methionine aminopeptidase

  摘要：

  With increasing emergence of multi-drug resistant infections, there is a dire need for new classes of compounds that act through unique mechanisms. In this work, we describe the discovery and optimization of a novel series of inhibitors of bacterial methionine aminopeptidase (MAP). Through a high-throughput screening campaign, one azepinone amide hit was found that resembled the native peptide substrate and possessed moderate biochemical potency against three bacterial isozymes. X-ray crystallography was used in combination with substrate-based design to direct the rational optimization of analogs with sub-micromolar potency. The novel compounds presented here represent potent broad-spectrum biochemical inhibitors of bacterial MAP and have the potential to lead to the development of new medicines to combat serious multi-drug resistant infections. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.061