3-bromo-4,5-diacetoxybenzoyl chloride | 122306-86-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 3-bromo-4,5-diacetoxybenzoyl chloride
• 英文别名: 5-Bromo-3,4-diacetoxybenzoyl chloride；(2-acetyloxy-3-bromo-5-carbonochloridoylphenyl) acetate
• CAS: 122306-86-9
• 化学式: C₁₁H₈BrClO₅
• 分子量: 335.539
• InChiKey: OJSLTJFYEQTSQR-UHFFFAOYSA-N

物化性质

• 沸点：
  423.7±45.0 °C(Predicted)
• 密度：
  1.618±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-bromo-4,5-diacetoxybenzoyl chloride 在 ammonium hydroxide 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-3-[[(3-bromo-4,5-dihydroxyphenyl)methylamino]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model

  摘要：

  Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta-half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2, = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pK(a) values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pK(a) was sufficiently acidic.

  DOI：

  10.1021/jm00092a015
• 作为产物：
  描述：

  3,4-diacetoxy-5-bromo-benzoic acid 在 氯化亚砜 作用下， 反应 0.33h， 以100%的产率得到3-bromo-4,5-diacetoxybenzoyl chloride
  参考文献：
  名称：

  Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model

  摘要：

  Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta-half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2, = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pK(a) values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pK(a) was sufficiently acidic.

  DOI：

  10.1021/jm00092a015

文献信息

• Cephalosporins, process for their preparation and pharmaceutical compositions
  申请人：ZENECA LIMITED

  公开号：EP0341948A2

  公开（公告）日：1989-11-15

  Cephalosporin antibiotics having a 3-position substituent of the formula: -CH₂NR¹-Y-A-Z-Q are described, wherein R¹ is hydrogen or certain optionally substituted alkyl groups; Y is -CO- or -SO₂-; A is optionally substituted phenylene or heterocyclylene; Z is a linking group and Q is a catechol or related ring system. Processes for their preparation and use are described.

  具有式中 3 位取代基的头孢菌素类抗生素： -Ch₂nr¹-y-a-z-q 其中 R¹ 是氢或某些任选取代的烷基；Y 是 -CO- 或 -SO₂-； A 是任选取代的亚苯基或杂环基； Z 是连接基团，Q 是邻苯二酚或相关环系。 描述了其制备和使用过程。
• Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues
  作者：J. C. Arnould、A. Bertrandie、T. G. C. Bird、D. Boucherot、F. Jung、J. J. Lohmann、A. Olivier、J. P. Bailey、W. Bell、G. M. Davies

  DOI：10.1021/jm00092a014

  日期：1992.7

  Cephalosporins with new catechol substituents at C-3' have been synthesized, including novel compounds with C-3' carbon-carbon bonds. Many of these compounds have high potency against Gram-negative bacteria, in particular against resistant strains like Pseudomonas aeruginosa. Structure-activity relationships are discussed in terms of their dependence on the pK(a) of the C-3' catechol and also in terms of steric and conformational factors of the C-3' substituent. The best overall properties were found in compounds with a bulky and/or conformationally restricted acidic C-3' catechol.
• Cephalosporin compounds, process for their preparation and their pharmaceutical compositions
  申请人：ZENECA Pharma S.A.

  公开号：EP0304155B1

  公开（公告）日：1995-11-15
• US5013730A
  申请人：——

  公开号：US5013730A

  公开（公告）日：1991-05-07
• US5055462A
  申请人：——

  公开号：US5055462A

  公开（公告）日：1991-10-08