(Z)-3-acetyl-1-(4-methoxyphenyl)-8-(2-(tritylamino)thiazol-4-yl)-2,6-dioxa-3,7-diazanon-7-en-9-oic acid | 941286-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (Z)-3-acetyl-1-(4-methoxyphenyl)-8-(2-(tritylamino)thiazol-4-yl)-2,6-dioxa-3,7-diazanon-7-en-9-oic acid
• CAS: 941286-37-9
• 化学式: C₃₆H₃₄N₄O₆S
• 分子量: 650.755
• InChiKey: XQHDSQGDPMEWBE-SCURRHDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.34
• 重原子数：
  47.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  122.58
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (Z)-3-acetyl-1-(4-methoxyphenyl)-8-(2-(tritylamino)thiazol-4-yl)-2,6-dioxa-3,7-diazanon-7-en-9-oic acid 在 三乙基硅烷 、 碳酸氢钠 、 三氟乙酸 、 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 、 二甲基亚砜 为溶剂， 生成 (S,Z)-3-(2-(2-aminothiazol-4-yl)-2-((2-(N-hydroxyacetamido)-ethoxy)imino)acetamido)-2,2-dimethyl-4-oxoazetidin-1-yl hydrogen sulfate
  参考文献：
  名称：

  Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections

  摘要：

  Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated mono-sulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4(1H)-one and the aminothiazole oxime were designed and synthesized. Structure activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound 12c) and methylthiomethyl (compound 16a) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound 12c exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound 12c shows an ED50 of 10.20 mg/kg. Taken together, the results indicate that compound 12c is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens.

  DOI：

  10.1021/acs.jmedchem.6b01261
• 作为产物：
  描述：

  tert-butyl [(4-methoxybenzyl)oxy]carbamate 在 盐酸 、 sodium hydride 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.5h， 生成 (Z)-3-acetyl-1-(4-methoxyphenyl)-8-(2-(tritylamino)thiazol-4-yl)-2,6-dioxa-3,7-diazanon-7-en-9-oic acid
  参考文献：
  名称：

  Synthesis and antibacterial activity of cephalosporins having hydroxamic acid at C-7 position

  摘要：

  The synthesis and in vitro activity of cephalosporins with hydroxamic acid at the 7-position are described. Anti-pseudomonal activity of the compound 11a was shown to be comparable to that of ceftazidime. Especially, the compound 11a exhibited good activity against Gram-positive bacteria including Streptococcus pneumoniae and Staphylococcus aureus. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00381-2