ethyl 2-formyl-7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate | 623932-13-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-formyl-7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate
• 英文别名: ethyl 2-formyl-7,8-dihydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate；ethyl 2-formyl-7,8-dihydropyrazolo[5',1':2,3][1,3]oxazolo[-5,4-c]pyridine-6(5H)-carboxylate；ethyl 4-formyl-7-oxa-2,3,10-triazatricyclo[6.4.0.02,6]dodeca-1(8),3,5-triene-10-carboxylate
• CAS: 623932-13-8
• 化学式: C₁₂H₁₃N₃O₄
• 分子量: 263.253
• InChiKey: DKTTUYJVGBVDHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-formyl-7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate 、 (5R,6S)-6-bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester 在 三乙胺 、 magnesium bromide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 4.0h， 生成
  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
• 作为产物：
  描述：

  ethyl 2-(hydroxymethyl)-7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate 在 二氧化锰 氮气 作用下， 以 氯仿 为溶剂， 反应 1.5h， 以1.43 g of the product was obtained (82%)的产率得到ethyl 2-formyl-7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-6(5H)-carboxylate
  参考文献：
  名称：

  Tricyclic 6-alkylidene-penems as β-lactamase inhibitors

  摘要：

  本发明提供了一种公式I的化合物、制药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。其中A和B中的一个表示氢，另一个表示可选取代的融合三环杂环基团；X为O。

  公开号：

  US07691842B2

文献信息

• [EN] HETEROTRICYCLYL 6-ALKYLIDENE-PENEMS AS BetaEpsilonTauAlpha-LACTAMASE INHIBITORS<br/>[FR] DERIVES D'HETEROTRICYCLYL 6-ALKYLIDENE-PENEMES EN TANT QU'INHIBITEURS DE BETA-LACTAMASE
  申请人：WYETH CORP

  公开号：WO2003093280A1

  公开（公告）日：2003-11-13

  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，药物组合物以及其用于治疗患有细菌感染或疾病的患者的用途。
• Tricyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
  申请人：Mansour Suhayl Tarek

  公开号：US20060276446A1

  公开（公告）日：2006-12-07

  This invention relates to certain tricyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. In accordance with the present invention there are provided compounds of formula I which are useful for treatment of bacterial infections having class-D enzymes associated therewith: wherein: One of A and B denotes hydrogen and the other an optionally substituted fused tricyclic heteroaryl group; and X is S or O.

  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。
• 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。