3-(aminomethyl)-7-<2-(2-aminothiazol-4-yl)-2-<(Z)-(1-carboxy-1-methylethoxy)imino>acetamido>ceph-3-em-4-carboxylic acid | 96628-33-0

• 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: 3-(aminomethyl)-7-<2-(2-aminothiazol-4-yl)-2-<(Z)-(1-carboxy-1-methylethoxy)imino>acetamido>ceph-3-em-4-carboxylic acid
• 英文别名: 7-<2-(2-aminothiazol-4-yl)-2-((Z)-1-carboxy-1-methylethoxyimino)acetamido>-3-aminomethylceph-3-em-4-carboxylic acid；3-(aminomethyl)-7-{2-(2-aminothiazol-4-yl)-2-[(Z)-(1-carboxy-1-methylethoxy)imino]acetamido}ceph-3-em-4-carboxylic acid；(6R,7R)-3-(aminomethyl)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 96628-33-0
• 化学式: C₁₇H₂₀N₆O₇S₂
• 分子量: 484.514
• InChiKey: HBFVBAVNGBCSBU-BIAHIMGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.99
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  210.53
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  3-(aminomethyl)-7-<2-(2-aminothiazol-4-yl)-2-<(Z)-(1-carboxy-1-methylethoxy)imino>acetamido>ceph-3-em-4-carboxylic acid 在 氨 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-3-[[(3,4-dihydroxyphenyl)sulfonylamino]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues

  摘要：

  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.

  DOI：

  10.1021/jm00092a014
• 作为产物：
  描述：

  (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-1-tert-butoxycarbonyl-1-methyl-ethoxyimino]-acetylamino}-3-azidomethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 镍 氢气 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 3-(aminomethyl)-7-<2-(2-aminothiazol-4-yl)-2-<(Z)-(1-carboxy-1-methylethoxy)imino>acetamido>ceph-3-em-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationships of cephalosporins with C-3' catechol-containing residues

  摘要：

  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.

  DOI：

  10.1021/jm00092a014

文献信息

• Synthesis and biological activity of C-3' ortho dihydroxyphthalimido cephalosporins.
  作者：MARIE-GENEVIÉVE BAUDART、LAURENT F. HENNEQUIN

  DOI：10.7164/antibiotics.46.1458

  日期：——

  A series of C-3' ortho dihydroxyphthalimido cephalosporins 3-7 has been prepared by reaction of C-3' aminomethyl cephalosporin 411). with the corresponding N-carboethoxyphthalimides 23-25, 37, 38. These new caphalosporins exhibit excellent in vitro Gram-negative activities, including Pseudomonas aeruginosa, excellent β-lactamases stability and pharmacokinetics equivalent or better than ceftriaxone.

  一系列C-3'邻二羟基酞酰亚胺甲基头孢菌素3-7通过C-3'氨基甲基头孢菌素411与相应的N-羰乙氧基酞酰亚胺23-25、37、38反应制备而成。这些新型头孢菌素显示出卓越的体外革兰氏阴性菌活性，包括铜绿假单胞菌，卓越的β-内酰胺酶稳定性，以及与头孢曲松相当或更优的药代动力学特性。
• Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model
  作者：T. G. C. Bird、J. C. Arnould、A. Bertrandie、F. H. Jung

  DOI：10.1021/jm00092a015

  日期：1992.7

  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.