7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde | 623564-27-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde
• 英文别名: 7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-3-carbaldehyde；(4-nitrophenyl)methyl 3-formyl-6,8-dihydro-5H-imidazo[1,2-a]pyrazine-7-carboxylate
• CAS: 623564-27-2
• 化学式: C₁₅H₁₄N₄O₅
• 分子量: 330.3
• InChiKey: ZHLRTNSBMCLQMM-UHFFFAOYSA-N

物化性质

• 沸点：
  627.2±55.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde 在 magnesium bromide 作用下， 以 四氢呋喃 为溶剂， 反应 23.5h， 生成 (5R)-6-[acetoxy-(7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester
  参考文献：
  名称：

  Mechanism of Inactivation of β-Lactamases by Novel 6-Methylidene Penems Elucidated Using Electrospray Ionization Mass Spectrometry

  摘要：

  The reactions of 6-methylidene penems 4-7 with beta-lactamases (TEM-1, SHV-1, Amp-C) were characterized by electrospray ionization mass spectrometry (ESI-MS). The kinetics of the reactions were monitored, demonstrating that only one penem. molecule reacts to form an acyl-enzyme complex. For penem 5, the ESI-MS/MS spectrum of the hydrolysis product produced in the reaction was identical to the spectrum generated from a synthesized dihydro[1,4]thiazepine 10, confirming the rearrangement of the penem ring system to a seven-membered dihydro[1,4]thiazepine structure. Gas-phase ESI-MS/MS fragmentation data were rationalized due to tautomerization between imine and enamine substructures. ESI-MS/MS analysis of the T-6 trypsin-digested fragments of TEM-1 and SHV-1 demonstrated that the penems were only attached to Ser-70 of these class A beta-lactamases and that the penem ring structures were rearranged to seven-membered dihydro[1,4]thiazepines.

  DOI：

  10.1021/jm049903j
• 作为产物：
  描述：

  2-imino-4-p-nitrobenzyloxycarbonyl piperazine 在 对甲苯磺酸 、 异丙醇 、 三乙胺 作用下， 以 环己烷 、 乙腈 、 乙酸乙酯 为溶剂， 反应 4.5h， 以51.6%的产率得到7-p-nitrobenzyloxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde
  参考文献：
  名称：

  [EN] BICYCLIC 6-ALKYLIDENE-PENEMS AS ß-LACTAMASES INHIBITORS
  [FR] PENEMES 6-ALKYLIDENE BICYCLIQUES UTILISES EN TANT QU'INHIBITEURS DE ss-LACTAMASES

  摘要：

  本发明提供了一种化合物（I）的配方、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。

  公开号：

  WO2003093279A1

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式I化合物的方法，该化合物对治疗细菌感染或疾病有用。
• Bicyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
  申请人：Mansour Suhayl Tarek

  公开号：US20060276445A1

  公开（公告）日：2006-12-07

  This invention relates to certain bicyclic 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 general formula I or a pharmaceutically acceptable salt or in vivo hydrolyzable ester R 5 thereof: wherein: One of A and B denotes hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X═O or S.

  这项发明涉及某些具有双环6-烷基亚烯基青霉素结构的化合物，其作为D类酶的抑制剂。β-内酰胺酶水解β-内酰胺类抗生素，因此是细菌耐药的主要原因。本发明的化合物与β-内酰胺类抗生素结合后，将提供一种有效的治疗方法，用于治疗威胁生命的细菌感染。根据本发明，提供了一般式I的化合物，或其药学上可接受的盐或体内可水解的酯R5：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双环杂环芳基团；X＝O或S。
• [EN] PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE 6-ALKYLIDENE PENEM
  申请人：WYETH CORP

  公开号：WO2003093277A1

  公开（公告）日：2003-11-13

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

  本发明提供了一种制备化合物的方法，该化合物符合式（I），对于治疗细菌感染或疾病非常有用。
• Bicyclic 6-alkylidene-penems as beta-lactamase inhibitors
  申请人：Venkatesan Mudumbai Aranapakam

  公开号：US20060217361A1

  公开（公告）日：2006-09-28

  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.

  本发明提供了一种I式化合物、制药组合物以及其在治疗需要治疗细菌感染或疾病的患者中的应用。
• Bicyclic 6-Alkylidene-Penems as Beta-Lactamase Inhibitors
  申请人：Venkatesan Aranapakam Mudumbai

  公开号：US20080312203A1

  公开（公告）日：2008-12-18

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

  本发明提供了化合物I的公式，其中A和B中的一个为氢，另一个为可选取代的融合双环杂环芳基基团; X为O，制备该化合物的药物组合物以及将其用于治疗患有细菌感染或疾病的患者。