(2S,3R)-N,3-dihydroxy-2-[3-oxo-6-[2-(3-phenylphenyl)ethynyl]-1H-isoindol-2-yl]butanamide | 1202236-59-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-N,3-dihydroxy-2-[3-oxo-6-[2-(3-phenylphenyl)ethynyl]-1H-isoindol-2-yl]butanamide
• CAS: 1202236-59-6
• 化学式: C₂₆H₂₂N₂O₄
• 分子量: 426.472
• InChiKey: APCRICKLDKEDMG-OSPHWJPCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-2-溴甲基苯甲酸甲酯 在 双(乙腈)氯化钯(II) 、 dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 、 O-(叔丁基二甲基硅烷)羟胺 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 (2S,3R)-N,3-dihydroxy-2-[3-oxo-6-[2-(3-phenylphenyl)ethynyl]-1H-isoindol-2-yl]butanamide
  参考文献：
  名称：

  Design and synthesis of potent Gram-negative specific LpxC inhibitors

  摘要：

  Antibiotic resistant hospital acquired infections are on the rise, creating an urgent need for novel bactericidal drugs. Enzymes involved in lipopolysaccharide (LPS) biosynthesis are attractive antibacterial targets since LPS is the major structural component of the outer membrane of Gram-negative bacteria. Lipid A is an essential hydrophobic anchor of LPS and the first committed step in lipid A biosynthesis is catalyzed by a unique zinc dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). LpxC is an attractive Gram-negative only target that has been chemically validated by potent bactericidal hydroxamate inhibitors that work by coordination of the enzyme's catalytic zinc ion. An exploratory chemistry effort focused on expanding the SAR around hydroxamic acid zinc-binding 'warheads' lead to the identification of novel compounds with enzyme potency and antibacterial activity similar to CHIR-090. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.111

文献信息

• SYNTHESIS AND USE OF HETEROCYCLIC ANTIBACTERIAL AGENTS
  申请人：Reddy Panduranga Adulla P.

  公开号：US20110212078A1

  公开（公告）日：2011-09-01

  This invention relates to compounds of the following Formula (I); or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, which is useful for the treatment of diseases or conditions mediated by LpxC.
• Design and synthesis of potent Gram-negative specific LpxC inhibitors
  作者：U. Faruk Mansoor、Dilrukshi Vitharana、Panduranga Adulla Reddy、Dayna L. Daubaras、Paul McNicholas、Peter Orth、Todd Black、M. Arshad Siddiqui

  DOI：10.1016/j.bmcl.2010.12.111

  日期：2011.2

  Antibiotic resistant hospital acquired infections are on the rise, creating an urgent need for novel bactericidal drugs. Enzymes involved in lipopolysaccharide (LPS) biosynthesis are attractive antibacterial targets since LPS is the major structural component of the outer membrane of Gram-negative bacteria. Lipid A is an essential hydrophobic anchor of LPS and the first committed step in lipid A biosynthesis is catalyzed by a unique zinc dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). LpxC is an attractive Gram-negative only target that has been chemically validated by potent bactericidal hydroxamate inhibitors that work by coordination of the enzyme's catalytic zinc ion. An exploratory chemistry effort focused on expanding the SAR around hydroxamic acid zinc-binding 'warheads' lead to the identification of novel compounds with enzyme potency and antibacterial activity similar to CHIR-090. (c) 2010 Elsevier Ltd. All rights reserved.