4-Nitrobenzyl (1S,5R,6S)-2-[6-(3-bromomethyl-benzyl)-7-methylthioimidazo[5,1-b]thiazolium-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate bromide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 4-Nitrobenzyl (1S,5R,6S)-2-[6-(3-bromomethyl-benzyl)-7-methylthioimidazo[5,1-b]thiazolium-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate bromide
• 英文别名: 4-Nitrobenzyl (1s,5r,6s)-2-[6-(3-bromomethyl-benzyl)-7-methylthioimidazo[5,1-b]thiazolium-2-yl]-6-((1r)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate bromide；(4-nitrophenyl)methyl (4S,5R,6S)-3-[6-[[3-(bromomethyl)phenyl]methyl]-7-methylsulfanylimidazo[5,1-b][1,3]thiazol-6-ium-2-yl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;bromide
• 化学式: Br*C₃₁H₃₀BrN₄O₆S₂
• 分子量: 778.542
• InChiKey: SXWMDYVSUNRBGR-PZZBZYFPSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.18
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  175
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  亚乙基硫脲 、 4-Nitrobenzyl (1S,5R,6S)-2-[6-(3-bromomethyl-benzyl)-7-methylthioimidazo[5,1-b]thiazolium-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate bromide 生成 (1S,5R,6S)-2-[6-[3-(4,5-Dihydro-1H-imidazol-2-yl)thiomethylbenzyl]-7-methylthioimidazo-[5,1-b]thiazolium-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate
  参考文献：
  名称：

  Novel carbapenem derivatives of quarternary salt type

  摘要：

  本发明的目的在于提供对MRSA、PRSP、流感病毒和β-内酰胺酶产生菌具有强大抗生素活性的碳青霉烯衍生物，且对DHP-1稳定。根据本发明的化合物是由公式(I)表示的化合物或其药物可接受的盐：1其中R1代表H或甲基；R2和R3各自独立地代表H、卤素、低级烷基等；R4代表可选地取代的低级烷基亚磺酰基等；R5代表可选地取代的低级烷基等。

  公开号：

  US20030022881A1
• 作为产物：
  描述：

  4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-(7-methylthioimidazo-[5,1-b]thiazol-2-yl)-1-carbapen-2-em-3-carboxylate 、 间二溴苄 生成 4-Nitrobenzyl (1S,5R,6S)-2-[6-(3-bromomethyl-benzyl)-7-methylthioimidazo[5,1-b]thiazolium-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate bromide
  参考文献：
  名称：

  CP5484, a novel quaternary carbapenem with potent anti-MRSA activity and reduced toxicity

  摘要：

  A new series of 1 beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5, 1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and the activities of these compounds against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. To study the effect of basic moieties on anti-MRSA activity, we introduced an amino, or imino, or amidino group at the 6-position of imidazo[5,1-b]thiazole in place of the carbamoylmethyl moiety of CP5068. Anti-MRSA activities of almost all basic group-substituted carbapenems were improved, though some of the compounds showed stronger acute toxicity in mice than IPM. In order to decrease the toxicity without decreasing the activity, we introduced various additional functionalities around the basic moiety. Finally, we obtained CP5484, which has excellent anti-MRSA activity and low acute toxicity. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.06.057

文献信息

• NOVEL CARBAPENEM DERIVATIVES OF QUATERNARY SALT TYPE
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1251134A1

  公开（公告）日：2002-10-23

  An objective of the present invention is to provide carbapenem derivatives which have potent antibiotic activity against MRSA, PRSP, Influenzavirus, and β-lactamase-producing bacteria and are stable against DHP-1. The compounds according to the present invention are compounds represented by formula (I) or pharmaceutically acceptable salts thereof: wherein R1 represents H or methyl; R2 and R3 each independently represent H, halogen, lower alkyl or the like; R4 represents optionally substituted lower alkylthio or the like; and R5 represents optionally substituted lower alkyl or the like.

  本发明的目的是提供碳青霉烯类衍生物，它们对 MRSA、PRSP、流感病毒和产 β-内酰胺酶细菌具有强效抗生素活性，并且对 DHP-1 稳定。根据本发明的化合物是由式（I）代表的化合物或其药学上可接受的盐： 其中 R1 代表 H 或甲基；R2 和 R3 各自独立地代表 H、卤素、低级烷基或类似物；R4 代表任选取代的低级烷硫基或类似物；R5 代表任选取代的低级烷基或类似物。
• Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity
  作者：Takahisa Maruyama、Yasuo Yamamoto、Yuko Kano、Mizuyo Kurazono、Eiki Shitara、Katsuyoshi Iwamatsu、Kunio Atsumi

  DOI：10.1016/j.bmcl.2008.11.039

  日期：2009.1

  A new series of 1 beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility. (C) 2008 Elsevier Ltd. All rights reserved.