N-[(1s,2r)-2-Hydroxy-1-(Hydroxycarbamoyl)propyl]-4-[4-(Phenylethynyl)phenyl]piperidine-1-Carboxamide | 1207183-69-4

• 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: N-[(1s,2r)-2-Hydroxy-1-(Hydroxycarbamoyl)propyl]-4-[4-(Phenylethynyl)phenyl]piperidine-1-Carboxamide
• 英文别名: N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-[4-(2-phenylethynyl)phenyl]piperidine-1-carboxamide
• CAS: 1207183-69-4
• 化学式: C₂₄H₂₇N₃O₄
• 分子量: 421.496
• InChiKey: SRSVRACVPWREJZ-VGSWGCGISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  O-(tert-butyl)-N-((4-nitrophenoxy)carbonyl)-L-threonine tert-butyl ester 在 O-(叔丁基二甲基硅烷)羟胺 、 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 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-[(1s,2r)-2-Hydroxy-1-(Hydroxycarbamoyl)propyl]-4-[4-(Phenylethynyl)phenyl]piperidine-1-Carboxamide
  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

• [EN] UREA DERIVATIVES AS ANTIBACTERIAL AGENTS<br/>[FR] DÉRIVÉS D'URÉE EN TANT QU'AGENTS ANTIBACTÉRIENS
  申请人：SCHERING CORP

  公开号：WO2010017060A1

  公开（公告）日：2010-02-11

  This invention relates to compounds of the 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.

  这项发明涉及以下化合物的结构（I）：或其药用盐、溶剂合物、酯或异构体，用于治疗由LpxC介导的疾病或症状。
• 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.