4-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 623931-46-4

• 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: 4-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• 英文别名: (4-nitrophenyl)methyl (5R)-6-[acetyloxy(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 623931-46-4
• 化学式: C₂₅H₂₁BrN₄O₇S₂
• 分子量: 633.5
• InChiKey: KAVALDJLVJKCNZ-JKJRPBHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  190
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 在 锌 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.0h， 以20%的产率得到(5R),(6Z)-7-oxo-6-(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-ylmethylene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Tricyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors

  摘要：

  这项发明涉及某些三环6-烷基亚胺基青霉素，其作为类D酶的抑制剂。β-内酰胺酶水解β-内酰胺类抗生素，因此是细菌抗药性的主要原因。本发明的化合物与β-内酰胺类抗生素结合时，将提供一种有效治疗危及生命的细菌感染的方法。根据本发明，提供了以下公式I的化合物，其用于治疗与类D酶相关的细菌感染：其中：A和B中的一个表示氢，另一个表示可选择取代的融合三环杂芳基团；X为S或O。

  公开号：

  US20060276446A1
• 作为产物：
  描述：

  、 乙酸酐 以 四氢呋喃 、 乙腈 为溶剂， 反应 15.0h， 以980 mg的产率得到4-nitrobenzyl (5R)-6-[(acetyloxy)(5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  5,5,6-Fused tricycles bearing imidazole and pyrazole 6-methylidene penems as broad-spectrum inhibitors of β-lactamases

  摘要：

  beta-Lactamases are serine- and metal-dependent hydrolases, produced by the bacteria as defense against beta-lactam antibiotics. Commercially available inhibitors such as clavulanic acid, sulbactam, and tazobactam, which are currently used in the hospital settings, have reduced activity against newly emerging beta-lactamases. Bacterial production of diverse beta-lactamases including class-A, class-C, and ESBLs has motivated several research groups to search for inhibitors with a broader spectrum of activity. Previously, several novel 6-methylidene penems bearing, [5, 5] [5, 6] and [5, 5, 5] heterocycles have been synthesized in our laboratory and were shown to be potent and broad-spectrum beta-lactamase inhibitors. As a continuation of our previous work and in order to extend the structure-activity relationships, in this paper, we describe herein the synthesis and in vitro, in vivo activities of several novel 5,5,6-fused tricyclic heterocycles attached to the 6-methylidene penem core. The compounds presented in the current paper are potent and broad-spectrum inhibitors of the TEM-1 and AmpC beta-lactamases. In combination with piperacillin, their in vitro activities showed enhanced susceptibility to class A- and C-resistant strains studied in various bacteria. Some of the newly synthesized compounds such as 12a-c were shown to have in vivo activity in the acute lethal infection model against TEM-1 producing organisms. The 5,5,6-fused heterocyclic ring cores such as 21, 25, and 35 reported here are hitherto unknown in the literature. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.006

文献信息

• Process for preparing 6-alkylidene penem derivatives
  申请人：Wyeth

  公开号：US20040132708A1

  公开（公告）日：2004-07-08

  The present invention provides a process of making compounds of formula I, which are useful for the treatment of bacterial infection or disease. 1

  本发明提供了一种制备I式化合物的方法，该化合物对于治疗细菌感染或疾病非常有用。
• Tricyclic 6-alkylidene-penems as beta-lactamase inhibitors
  申请人：Wyeth

  公开号：US20040043978A1

  公开（公告）日：2004-03-04

  The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof. 1

  本发明提供了一种化合物I，药物组合物及其用于治疗需要治疗细菌感染或疾病的患者的用途。
• Tricyclic 6-Alkylidene-Penems as Beta-Lactamase Inhibitors
  申请人：Venkatesan Aranapakam Mudumbai

  公开号：US20080318921A1

  公开（公告）日：2008-12-25

  The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

  本发明提供了一种I式化合物、药物组合物及其在治疗需要治疗细菌感染或疾病的患者中的用途。
• Tricyclic 6-alkylidene-penems as β-lactamase inhibitors
  申请人：Wyeth

  公开号：US07018997B2

  公开（公告）日：2006-03-28

  The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof. wherein one of A and B denotes hydrogen and the other an optionally substituted fused tricyclic heteroaryl group; and X is S.

  本发明提供了一种I式化合物，以及用于治疗需要治疗细菌感染或疾病的患者的药物组合物和使用方法。其中，A和B中的一个表示氢，另一个表示可选择取代的融合三环杂环基团；X为S。