2-bromo-4,5-diacetoxy-(E)-cinnamyl chloride | 141555-23-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-bromo-4,5-diacetoxy-(E)-cinnamyl chloride
• 英文别名: [2-acetyloxy-4-bromo-5-[(E)-3-chloro-3-oxoprop-1-enyl]phenyl] acetate
• CAS: 141555-23-9
• 化学式: C₁₃H₁₀BrClO₅
• 分子量: 361.576
• InChiKey: GEICTOUPARUWNW-ONEGZZNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.15
• 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：

  2-bromo-4,5-diacetoxy-(E)-cinnamyl chloride 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-1-carboxy-1-methyl-ethoxyimino]-acetylamino}-3-{[(E)-3-(4,5-diacetoxy-2-bromo-phenyl)-acryloylamino]-methyl}-8-oxo-5-thia-1-aza-bicyclo[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：

  2-bromo-4,5-dihydroxy-(E)-cinnamic acid 在 氯化亚砜 、 硫酸 作用下， 反应 2.33h， 生成 2-bromo-4,5-diacetoxy-(E)-cinnamyl 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