ethyl 3-{[(3-ethoxycarbonyl)-1H-pyrazol-5-yl]oxy}-4-oxopiperidine-1-carboxylate | 623932-10-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 3-{[(3-ethoxycarbonyl)-1H-pyrazol-5-yl]oxy}-4-oxopiperidine-1-carboxylate
• 英文别名: ethyl 3-[(5-ethoxycarbonyl-1H-pyrazol-3-yl)oxy]-4-oxopiperidine-1-carboxylate
• CAS: 623932-10-5
• 化学式: C₁₄H₁₉N₃O₆
• 分子量: 325.321
• InChiKey: YQERAHUAKFXXBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  537.6±50.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-{[(3-ethoxycarbonyl)-1H-pyrazol-5-yl]oxy}-4-oxopiperidine-1-carboxylate 在 甲烷磺酸 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 反应 18.0h， 以57%的产率得到diethyl 7,8-tetrahydropyrazolo[5',1':2,3][1,3]oxazolo[5,4-c]pyridine-2,6(5H)-dicarboxylate
  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：

  3-溴-4-氧代哌啶-1-甲酸乙酯 、 5-酮-4,5-二氢-1H-吡唑-3-羧酸乙酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以19%的产率得到ethyl 3-{[(3-ethoxycarbonyl)-1H-pyrazol-5-yl]oxy}-4-oxopiperidine-1-carboxylate
  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

• [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。
• TRICYCLIC 6-ALKYLIDENE-PENEMS AS CLASS-D ß-LACTAMASES INHIBITORS
  申请人：Wyeth

  公开号：EP1885358A2

  公开（公告）日：2008-02-13
• [EN] TRICYCLIC 6-ALKYLIDENE-PENEMS AS CLASS-D ß-LACTAMASES INHIBITORS<br/>[FR] 6-ALKYLIDENE-PENEMS TRICYCLIQUES, INHIBITEURS DES ß-LACTAMASES DE CLASSE D
  申请人：WYETH CORP

  公开号：WO2007030166A2

  公开（公告）日：2007-03-15

  [EN] This invention relates to certain tricyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. ß-Lactamases hydrolyze ß-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with ß-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 (Formula I): wherein: One of A and B denotes hydrogen and the other an optionally substituted fused tricyclic heteroaryl group; and X is S or O.
  [FR] L'invention porte sur des 6-alkylidène-pénems tricycliques qui, agissant comme inhibiteurs des ß-lactamases de classe D, hydrolysent les antibiotiques de ß-lactame et, en tant que tels, sont la cause primaire de la résistance aux bactéries. Lesdits composés lorsque combinés aux antibiotiques de ß-lactame constituent un traitement efficace contre les infections bactériennes menaçant la vie. Les composés de l'invention, utiles pour le traitement d'infections bactériennes associées à des enzymes de classe D, présentent la formule (I) dans laquelle: l'un de A ou B est hydrogène, et l'autre, un groupe hétéroaryle tricyclique facultativement substitué, et X est S ou O.
• 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.