diphenylmethyl 7β-tert-butoxycarbonylamino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylate | 93068-78-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diphenylmethyl 7β-tert-butoxycarbonylamino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylate
• 英文别名: benzhydryl 7β-t-butoxycarbonylamino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylate；benzhydryl (6R,7R)-7-[(2-methylpropan-2-yl)oxycarbonylamino]-8-oxo-3-[(E)-2-pyridin-3-ylsulfanylethenyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 93068-78-1
• 化学式: C₃₂H₃₁N₃O₅S₂
• 分子量: 601.747
• InChiKey: LGDLRPRJNILXOF-GGZCUKSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 7β-tert-butoxycarbonylamino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylate 在 盐酸 、 甲酸 作用下， 反应 0.67h， 以95%的产率得到7β-amino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylic acid dihydrochloride
  参考文献：
  名称：

  Orally active cephalosporins. Part 2: Synthesis, structure–activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain

  摘要：

  A series of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00021-3
• 作为产物：
  描述：

  吡啶-3-硫醇 在 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 diphenylmethyl 7β-tert-butoxycarbonylamino-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylate
  参考文献：
  名称：

  Studies on Anti-MRSA Parenteral Cephalosporins. IV. A Novel Water-soluble N-Phosphono Type Prodrug for Parenteral Administration.

  摘要：

  描述了一种提高抗 MRSA（耐甲氧西林金黄色葡萄球菌）头孢菌素衍生物水溶性的系统方法。我们首先尝试提高7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-氟甲氧基亚氨基-乙酰氨基]-3-[(E)-的水溶性2-(1-甲基咪唑并[1, 2-b)]哒嗪鎓-6-基)硫乙烯基]-3-头孢烯-4-羧酸酯(1a)，通过取代C-3'药效团。用 1-甲基-4-吡啶基取代 C-3' 药效基团可提高水溶性，但不会降低抗 MRSA 活性。此外，我们将 N 修饰的前药策略应用于 C-7 酰基，以大幅提高水溶性。在制备的化合物中，N-膦酰基型前药2a（1-甲基咪唑[1,2-b]哒嗪鎓衍生物）和2b（1-甲基-4-吡啶衍生物）显示出适合静脉注射产品的水溶性体内抗MRSA活性与万古霉素相当。

  DOI：

  10.7164/antibiotics.54.364

文献信息

• Orally active cephalosporins. Part 2: Synthesis, structure–activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain
  作者：Hirofumi Yamamoto、Takeshi Terasawa、Ayako Nakamura、Kohji Kawabata、Kazuo Sakane、Satoru Matsumoto、Yoshimi Matsumoto、Shuichi Tawara

  DOI：10.1016/s0968-0896(00)00021-3

  日期：2000.5

  A series of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Studies on Anti-MRSA Parenteral Cephalosporins. IV. A Novel Water-soluble N-Phosphono Type Prodrug for Parenteral Administration.
  作者：TOMOYASU ISHIKAWA、YUTAKA NAKAYAMA、MITSUMI TOMIMOTO、SHIN-ICHI NIWA、KEIJI KAMIYAMA、SHOHEI HASHIGUCHI、YUJI IIZAWA、KENJI OKONOGI、AKIO MIYAKE

  DOI：10.7164/antibiotics.54.364

  日期：——

  A systematic approach for improving the water-solubility of anti-MRSA (methicillin-resistant Staphylococcus aureus) cephalosporin derivatives is described. We first tried to improve the water-solubility of 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-fluoromethoxyimino-acetamido]-3-[(E)-2-(1-methylimidazo[1, 2-b)]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (1a) by substitution of the C-3' pharmacophore. Replacement of the C-3' pharmacophore with a 1-methyl-4-pyridinio group improved the water-solubility without decreasing the anti-MRSA activity. Furthermore, we applied the N-modified prodrug strategy to the C-7 acyl group in order to enhance the water-solubility drastically. Among the compounds prepared, the N-phosphono type prodrugs 2a (1-methylimidazo[1, 2-b]pyridazinium derivative) and 2b (1-methyl-4-pyridinio derivative) showed water-solubility appropriate for a product intended for intravenous injection and in vivo anti-MRSA activity comparable to that of vancomycin.

  描述了一种提高抗 MRSA（耐甲氧西林金黄色葡萄球菌）头孢菌素衍生物水溶性的系统方法。我们首先尝试提高7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-氟甲氧基亚氨基-乙酰氨基]-3-[(E)-的水溶性2-(1-甲基咪唑并[1, 2-b)]哒嗪鎓-6-基)硫乙烯基]-3-头孢烯-4-羧酸酯(1a)，通过取代C-3'药效团。用 1-甲基-4-吡啶基取代 C-3' 药效基团可提高水溶性，但不会降低抗 MRSA 活性。此外，我们将 N 修饰的前药策略应用于 C-7 酰基，以大幅提高水溶性。在制备的化合物中，N-膦酰基型前药2a（1-甲基咪唑[1,2-b]哒嗪鎓衍生物）和2b（1-甲基-4-吡啶衍生物）显示出适合静脉注射产品的水溶性体内抗MRSA活性与万古霉素相当。