5,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-ylmethanol | 349481-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-ylmethanol
• CAS: 349481-45-4
• 化学式: C₁₀H₁₂N₂OS
• 分子量: 208.284
• InChiKey: PIUIKPWUVTXPEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-ylmethanol 在 manganese(IV) oxide 作用下， 生成 5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-2-carbaldehyde
  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：

  ethyl 7-thia-2,5-diazatricyclo[6.4.0.0^2,6]dodeca-1(8),3,5-triene-4-carboxylate 在 锂硼氢 作用下， 生成 5,6,7,8-Tetrahydroimidazo[2,1-b][1,3]benzothiazol-2-ylmethanol
  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

文献信息

• 5,5,6-Fused tricycles bearing imidazole and pyrazole 6-methylidene penems as broad-spectrum inhibitors of β-lactamases
  作者：Aranapakam M. Venkatesan、Atul Agarwal、Takao Abe、Hideki Ushirogochi、Mihira Ado、Takasaki Tsuyoshi、Osvaldo Dos Santos、Zhong Li、Gerry Francisco、Yang I. Lin

  DOI：10.1016/j.bmc.2007.11.006

  日期：2008.2.15

  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.