benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylate-4,4-dioxide | 76454-54-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylate-4,4-dioxide
• 英文别名: 6,6-dibromopenicillanic acid 1,1-dioxide benzyll ester；6,6-Dibromopenicillanic acid 1,1-dioxide benzyl ester；6,6-dibromosulbactam benzyl ester；benzyl 6,6-dibromopenicillanate 1,1-dioxide；benzyl 6,6-dibromo-1,1-dioxopenicillanate；benzyl 6,6-dibromopenicillanatesulfone；benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-4,4,7-trioxo-4lambda6-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate；benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-4,4,7-trioxo-4λ6-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 76454-54-1
• 化学式: C₁₅H₁₅Br₂NO₅S
• 分子量: 481.162
• InChiKey: QZVGVSQWJUUPMO-GXFFZTMASA-N

物化性质

• 熔点：
  146-147 °C
• 沸点：
  594.0±50.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  89.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylate-4,4-dioxide 生成 Benzyl 6-beta-Bromo-6-alpha-(Methoxyaminomethyl)penicillanate 1,1-Dioxide
  参考文献：
  名称：

  Beta-lactamase inhibiting 6-(alkoxyamino-methyl) penicillanic acid

  摘要：

  6-α/β-[(C.sub.1 -C.sub.4)烷氧基氨甲基和苄氧基氨甲基]青霉素酸1,1-二氧化物，其药用盐及在生理条件下可水解的常规酯，均可用于医学中作为β-内酰胺酶抑制剂；以及其中间体和相关工艺；以及将现有化合物转化为6-α和6-β-(氨基甲基)青霉素酸1,1-二氧化物和衍生物的工艺。

  公开号：

  US04499017A1
• 作为产物：
  描述：

  benzyl 6,6-dibromopenicillanate 在 potassium permanganate 作用下， 生成 benzyl (2S,5R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]-heptane-2-carboxylate-4,4-dioxide
  参考文献：
  名称：

  Stereoselective Preparation of 6-b-Bromopenicillanic Acid Derivatives

  摘要：

  A new stereoselective method for the preparation of 6-beta-bromopenicillanates is described. It comprises the reaction of 6,6-dibromopenicillanates with silver nitrate in 2-propanol.

  DOI：

  10.3987/com-94-6898

文献信息

• [EN] BETA-LACTAMASE INHIBITOR PRODRUG<br/>[FR] PROMEDICAMENT INHIBITEUR DE LA BETA-LACTAMASE
  申请人：PFIZER PROD INC

  公开号：WO2004108733A1

  公开（公告）日：2004-12-16

  Prodrugs of 6-β-hydroxymethylpenicillanic acid sulfone having the structure wherein R is H or methyl, each X is methylene, and Y is 0, or wherein R is H, each X is 0 and Y is methylene, and solvates thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a prodrug of the present invention, or a solvate thereof, an optional beta-lactam antibiotic and at least one pharmaceutically acceptable carrier. Further disclosed is a method for increasing the therapeutic effectiveness of a beta-lactam antibiotic in 20 a mammal by administering an effective amount of a beta­lactam antibiotic and an effectiveness-increasing amount of a prodrug of the present invention, or a solvate thereof. Additionally disclosed is a method for treating a bacterial infection in a mammal by administering a therapeutically effective amount of a pharmaceutical composition of the present invention to a mammal in need thereof.

  6-β-羟甲基青霉烷酸磺酸的前药具有以下结构，其中R为H或甲基，每个X为亚甲基，Y为0，或其中R为H，每个X为0，Y为亚甲基，以及其溶剂化合物。还披露了包括本发明的前药或其溶剂化合物、可选的β-内酰胺类抗生素和至少一种药用可接受载体的药物组合物。进一步披露了通过给哺乳动物投予有效量的β-内酰胺类抗生素和本发明的前药或其溶剂化合物的增效量来增加β-内酰胺类抗生素的治疗效果的方法。此外，还披露了通过给需要的哺乳动物投予本发明的药物组合物的治疗有效量来治疗哺乳动物的细菌感染的方法。
• [EN] BETA-LACTAMASE INHIBITOR PRODRUG<br/>[FR] PROMEDICAMENT INHIBITEUR DE BETA-LACTAMASE
  申请人：PFIZER PROD INC

  公开号：WO2004018484A1

  公开（公告）日：2004-03-04

  Prodrugs of 6-ß-hydroxymethylpenicillanic acid sulfone having the structure wherein R is H or methyl, and solvates thereof, are disclosed. Also disclosed are pharmaceutical compositions comprising a prodrug of the present invention, or a solvate thereof, an optional beta-lactam antibiotic and at least one pharmaceutically acceptable carrier. Further disclosed is a method for increasing the therapeutic effectiveness of a beta-lactam antibiotic in a mammal by administering an effective amount of a betalactam antibiotic and an effectiveness-increasing amount of a prodrug of the present invention, or a solvate thereof. Additionally disclosed is a method for treating a bacterial infection in a mammal by administering a therapeutically effective amount of a pharmaceutical composition of the present invention to a mammal in need thereof.

  6-ß-羟甲基青霉烷酸磺酸酯的前药具有结构，其中R为H或甲基，并公开其溶剂合物。还公开了包括本发明的前药或其溶剂合物、可选的β-内酰胺类抗生素和至少一种药用载体的药物组合物。进一步公开了通过给哺乳动物投予β-内酰胺类抗生素的有效量和本发明的前药或其溶剂合物的增效量来增加β-内酰胺类抗生素的治疗效果的方法。此外，还公开了通过给需要的哺乳动物投予本发明的药物组合物的治疗有效量来治疗哺乳动物的细菌感染的方法。
• 6-(Substituted)methylene-penicillanic and
  申请人：Pfizer Inc.

  公开号：US04826833A1

  公开（公告）日：1989-05-02

  Beta-lactamase inhibiting compounds of the formula ##STR1## or a pharmaceutically acceptable acid addition or carboxylate salt thereof; where n is zero, 1 or 2; X.sub.3 is H or Br, R.sup.1 is H, the residue of certain carboxy-protecting groups or the residue of an ester group readily hydrolyzable in vivo; one of R.sup.12 and R.sup.13 is H and the other is vinyl, certain aryl, alkylthio, alkylsulfonyl or certain heterocyclyl, aminomethyl, thiocarboxamido or amidino groups; one or R.sup.2 and R.sup.3 is H and the other is as disclosed for the other of R.sup.12 and R.sup.13, or is Cl or CH.sub.2 OH, and R.sup.18 is H or certain acyl groups; intermediates useful in their production, methods for their preparation and use, and pharmaceutical compositions containing them.

  β-内酰胺酶抑制化合物的结构式为##STR1##或其药学上可接受的酸加合物或羧酸盐；其中n为零、1或2；X.sub.3为H或Br，R.sup.1为H，某些羧基保护基的残基或在体内容易水解的酯基残基；R.sup.12和R.sup.13中的一个为H，另一个为乙烯基、某些芳基、烷基硫基、烷基磺酰基或某些杂环基、氨甲基、硫代羧酰胺基或胍基；R.sup.2和R.sup.3中的一个为H，另一个如R.sup.12和R.sup.13的另一个所披露的，或为Cl或CH.sub.2 OH，R.sup.18为H或某些酰基；在其生产中有用的中间体、其制备和使用的方法，以及含有它们的药物组合物。
• 6-(Aminomethyl)penicillanic acid 1,1-dioxide esters and intermediates
  申请人：Pfizer Inc.

  公开号：US04536393A1

  公开（公告）日：1985-08-20

  6-alpha- and 6-beta-(Aminomethyl)penicillanic acid, 1,1-dioxide esters which are hydrolyzable under physiological conditions, particularly those wherein the ester radical is 1H-isobenzofuran-3-on-1-yl or (5-methyl-1,3-dioxol-2-on-4-yl)methyl, and an improved process and intermediates used in their synthesis.

  6-alpha-和6-beta-(氨甲基)青霉酸，1,1-二氧化酯在生理条件下可水解，特别是其中酯基为1H-异苯并呋喃-3-酮-1-基或(5-甲基-1,3-二氧杂环-2-酮-4-基)甲基，以及用于它们合成的改进工艺和中间体。
• A New Efficient Stereoselective Debromination Reaction with Trialkylgermanium Hydrides Useful in the Design of Short Synthetic Routes to β-Lactamase Inhibitor Prodrugs
  作者：Timothy Norris、Christian Dowdeswell、Natalka Johnson、Dan Daia

  DOI：10.1021/op050151s

  日期：2005.11.1

  suitable for prodrug use in high yields. The bromine abstraction usually results in favoured formation of the 6-β-hydroxymethyl epimer relative to the 6-α-hydroxymethyl epimer in ratios that exceed 97:3. Reaction of pure 6-α-hydroxymethyl-6-β-bromo-penicillate-1,1-dioxide ester results in almost exclusive formation of 6-β-hydroxymethylsulbactam ester. This methodology conserves the C−C bond formation at C-6

  从β内酰胺酶抑制剂6-β-hydroxymethylsulbactam衍生的前药能够有效地在三个步骤通过使利用三的高度立体选择性的自由基脱溴使用合成Ñ-丁基氢化锗。该试剂能够从高产率的适合于前药使用的差向异构体6-羟基甲基-6-溴青霉酸酯-1,1-二氧化物酯和官能化酯对的C-6位置提取溴。相对于6-α-羟甲基差向异构体，比率超过97∶3，溴的提取通常导致6-β-羟甲基差向异构体的有利形成。纯的6-α-羟甲基-6-β-溴青霉酸酯-1,1-二氧化物酯的反应导致几乎完全形成6-β-羟甲基舒巴坦酯。该方法通过利用甲酰化反应产生的两种差向异构体来保护C-6处的C-C键形成，这在β-羟甲基舒巴坦前药合成中既困难又非立体选择性。