diphenylmethyl 7β-[(Z)-2-(2-formamidothiazol-4-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate | 454472-38-9

• 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: diphenylmethyl 7β-[(Z)-2-(2-formamidothiazol-4-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate
• CAS: 454472-38-9
• 化学式: C₅₇H₅₃N₇O₈S₃
• 分子量: 1060.29
• InChiKey: YAZNZGHZXRSMAS-BEMKLVQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.47
• 重原子数：
  75.0
• 可旋转键数：
  19.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  183.41
• 氢给体数：
  2.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 7β-[(Z)-2-(2-formamidothiazol-4-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以63%的产率得到diphenylmethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-[(4-pyrazolyl)methylthio]-3-cephem-4-carboxylate
  参考文献：
  名称：

  Orally Active Cephalosporins. Part 4: Synthesis, Structure–Activity Relationships and Oral Absorption of Novel 3-(4-Pyrazolylmethylthio)cephalosporins with Various C-7 Side Chains

  摘要：

  A series of 3-(4-pyrazolylmethylthio)cephalosporins with various C-7 side chains was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity against Haemophilus influenzae was markedly increased by the C-7 oxime moiety. Deamination at the 2 position of, or introduction of a substituent such as halogen or methyl to, the 5 position of the (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) moiety improved oral absorption. Among these compounds, FR192752 (40a) having a (Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-hydroxyiminoacetam do moiety, showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including H. influenzae and penicillin G-resistant Streptococcus pneumoniae (PRSP). Further, it showed higher oral absorption than CFDN and FK041. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00416-3
• 作为产物：
  描述：

  7β-amino-3-methanesulfonyloxycephem 在 sodium hydrogensulfide 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 diphenylmethyl 7β-[(Z)-2-(2-formamidothiazol-4-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate
  参考文献：
  名称：

  Orally Active Cephalosporins. Part 4: Synthesis, Structure–Activity Relationships and Oral Absorption of Novel 3-(4-Pyrazolylmethylthio)cephalosporins with Various C-7 Side Chains

  摘要：

  A series of 3-(4-pyrazolylmethylthio)cephalosporins with various C-7 side chains was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity against Haemophilus influenzae was markedly increased by the C-7 oxime moiety. Deamination at the 2 position of, or introduction of a substituent such as halogen or methyl to, the 5 position of the (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) moiety improved oral absorption. Among these compounds, FR192752 (40a) having a (Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-hydroxyiminoacetam do moiety, showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including H. influenzae and penicillin G-resistant Streptococcus pneumoniae (PRSP). Further, it showed higher oral absorption than CFDN and FK041. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00416-3