p-nitrobenzyl 2-<2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl>-2-isopropenylacetate | 95122-89-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: p-nitrobenzyl 2-<2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl>-2-isopropenylacetate
• 英文别名: p-nitrobenzyl (2R)-2-[(3S,4R)-4-(benzothiazol-2-yldithio)-3-bromo-2-oxoazetidin-1-yl]-3-methylbut-3-enoate；p-nitrobenzyl 2-[2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl]-2-isopropenylacetate；(4-Nitrophenyl)methyl (I+/-R,2R,3S)-2-(2-benzothiazolyldithio)-3-bromo-I+/--(1-methylethenyl)-4-oxo-1-azetidineacetate；(4-nitrophenyl)methyl (2R)-2-[(2R,3S)-2-(1,3-benzothiazol-2-yldisulfanyl)-3-bromo-4-oxoazetidin-1-yl]-3-methylbut-3-enoate
• CAS: 95122-89-7
• 化学式: C₂₂H₁₈BrN₃O₅S₃
• 分子量: 580.504
• InChiKey: UPVOZBVZWJUNLP-NLWGTHIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  184
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  p-nitrobenzyl 2-<2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl>-2-isopropenylacetate 在 乙酰胺 、 溴 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以1.13 g的产率得到p-nitrobenzyl 6α-bromo-2β-(bromomethyl)-2α-methylpenam-3α-carboxylate
  参考文献：
  名称：

  Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-[(acyloxy)methyl]-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxides

  摘要：

  p-Nitrobenzyl 2 beta-[(benzoyloxy)methyl]-2 alpha-methylpenam-3 alpha-carboxylate was prepared by reaction of p-nitrobenzyl 2-[2-oxo-3 alpha-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl] -2-isopropenylacetate with silver benzoate in the presence of iodine. The resulting diester was oxidized to the sulfone with potassium permanganate and hydrogen peroxide, and the bromine and p-nitrobenzyl groups were removed by hydrogenolysis to give potassium 2 beta-(benzoyloxy)methyl 2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide. A series of related compounds, including the pivaloyl, methoxybenzoyl, p-fluorobenzoyl, and p-aminobenzoyl derivatives, were prepared in a similar way. All of these compounds were potent beta-lactamase inhibitors in vitro against the TEM beta-lactamase from Klebsiella pneumoniae A22695 and Bacteroides fragiles A22695 but less active against the beta-lactamase from Staphylococcus aureus A9606. All compounds when administered orally in a 1:1 combination with amoxicillin did not show any significant protection of mice infected with S. aureus A9606. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid was prepared and reacted with silver nitrate to give the nitrate ester. Oxidation with potassium permanganate and catalytic reduction afforded 2 beta-(hydroxymethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide was found to be a strong beta-lactamase inhibitor, while the 2 beta-hydroxymethyl compound showed only weak beta-lactamase-inhibiting properties.

  DOI：

  10.1021/jm00382a025
• 作为产物：
  描述：

  6-aminopenicillanic acid 在 氢溴酸 、 potassium carbonate 、 间氯过氧苯甲酸 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.42h， 生成 p-nitrobenzyl 2-<2-oxo-3α-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl>-2-isopropenylacetate
  参考文献：
  名称：

  一种新颖，温和且简便的方法来制备6-亚甲基Penem衍生物

  摘要：

  建立了一种新颖且温和的方法来合成6-亚甲基青霉烯化合物。该方法需要在6-溴openem 12上用适当取代的醛在M- Br 2 / Et 3 N上促进的Aldol型缩合反应，生成中间体乙酰化的溴代醇，将其平滑地转化为最终产物，同时使用C3羧酸酯进行脱保护pH 6.5的活性锌粉尘和磷酸盐缓冲液。该方法为青霉素衍生物的CC键形成方法提供了有用的变化，并且还用作制备6-外亚甲基青霉烯衍生物而在C5位不消旋的实用合成方法。

  DOI：

  10.1021/jo049880g

文献信息

• [EN] PYRROLE BASED INHIBITORS OF GLYCOGEN SYNTHASE KINASE 3<br/>[FR] INHIBITEURS DE LA GLYCOGENE SYNTHASE KINASE 3 A BASE DE PYRROLE
  申请人：CHIRON CORP

  公开号：WO2004018455A1

  公开（公告）日：2004-03-04

  New pyrrole based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

  提供了基于新吡咯烷基化合物的方法、组合物以及抑制体外糖原合成酶激酶（GSK3）活性和治疗体内GSK3介导的疾病的方法。该发明的方法、化合物和组合物可单独使用，也可与其他药理活性剂结合在一起，用于治疗由GSK3活性介导的疾病，如糖尿病、阿尔茨海默病和其他神经退行性疾病、肥胖、动脉粥样硬化心血管疾病、原发性高血压、多囊卵巢综合征、X综合征、缺血、创伤性脑损伤、躁狂抑郁症、免疫功能缺陷或癌症。
• 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。
• [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。
• PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES
  申请人：Wyeth

  公开号：EP1499620A1

  公开（公告）日：2005-01-26
• PYRROLE BASED INHIBITORS OF GLYCOGEN SYNTHASE KINASE 3
  申请人：CHIRON CORPORATION

  公开号：EP1537099A1

  公开（公告）日：2005-06-08