ceftaroline | 189345-04-8

• 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: ceftaroline
• 英文别名: T-91825；CPT；(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetyl]amino]-3-[[4-(1-methylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 189345-04-8
• 化学式: C₂₂H₂₀N₈O₅S₄
• 分子量: 604.715
• InChiKey: RGFBRLNVZCCMSV-BIRGHMBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  287
• 氢给体数：
  2
• 氢受体数：
  14

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：尽管没有关于母乳喂养期间使用头孢洛林的资料，但一般来说，头孢菌素类药物不太可能在哺乳婴儿中引起不良反应。偶尔有报道头孢菌素类药物会破坏婴儿的胃肠道菌群，导致腹泻或鹅口疮，但这些影响尚未得到充分评估。头孢洛林在哺乳期母亲中是可以接受的。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Although no information is available on the use of ceftaroline during breastfeeding, cephalosporins are generally not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Ceftaroline is acceptable in nursing mothers. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 吡啶 、 ceftaroline 、 丙酮 以 N,N-二甲基乙酰胺 为溶剂， 反应 22.0h， 以to afford 97 g of crude (6R,7R)-7-[[(2Z)-2-(ethoxyimino)-2-[5-(acetamido)-1,2,4-thiadiazol-3-yl]acetyl]amino]-3-[[4-(1-methylpyridinium-4-yl)-1,3-thiazol-2-yl]sulfanyl]-8-oxo-5-thia-1-azabicylo[4.2.0]oct-2-ene-2-carboxylate的产率得到(6R,7R)-7-[[(2Z)-2-(5-acetamido-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetyl]amino]-3-[[4-(1-methylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  Cephem compounds useful for the treatment of bacterial infections

  摘要：

  本发明涉及一种新的头孢菌素化合物，用于治疗式I的细菌感染：本发明还涉及制备该化合物的方法、包含该化合物的药物组合物以及使用该化合物的治疗方法。这些新的头孢菌素化合物稳定，溶解性好，特别适合于例如静脉注射治疗细菌感染。

  公开号：

  US08247400B2
• 作为产物：
  描述：

  (7R)-7-[(phenylacetyl)amino]-3-trifluoromethanesulfonyloxy-3-cephem-4-carboxylate, 4-methoxybenzyl ester 在 吡啶 、 五氯化磷 、 sodium hydride 、 碳酸氢钠 、 苯甲醚 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 ceftaroline
  参考文献：
  名称：

  TAK-599, a novel N-Phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties

  摘要：

  Crystalline 1 (TAK-599) is a novel N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin 2a (T-91825) that has high affinity for penicillin-binding protein (PBP) 2' (IC50; 0.90 mug/mL) and shows potent in vitro anti-MRSA activity (MIC against MRSA N133; 1.56 mug/mL), comparable to that of vancomycin (1.56 mug/mL). Although 2a had insufficient water solubility (2.3 mg/mL) for parenteral administration, 1 showed excellent water solubility (> 100 mg/mL, pH 7) as well as good chemical stability in the solid state and solution. In pharmacokinetic studies, when 1 was administered intravenously to rats and monkeys, it was rapidly converted into 2a in the blood. These results show that 1 (TAK-599) is a highly promising parenteral cephalosporin targeted for MRSA infection. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00126-3

文献信息

• NOVEL CEPHEM COMPOUNDS USEFUL FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：Dedhiya Mahendra G.

  公开号：US20100216745A1

  公开（公告）日：2010-08-26

  The present invention relates to new cephem compounds useful for the treatment of bacterial infections. The invention also relates to methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and to methods of treatment using the compounds. The new cephem compounds are stable, exhibit good solubility, and are particularly well suited for, e.g., parenteral administration for the treatment of bacterial infections.

  本发明涉及一种新的头孢菌素化合物，可用于治疗细菌感染。本发明还涉及制备该化合物的方法、包含该化合物的药物组合物，以及使用该化合物进行治疗的方法。这些新的头孢菌素化合物稳定，溶解性好，特别适用于例如静脉注射治疗细菌感染等情况。
• US8247400B2
  申请人：——

  公开号：US8247400B2

  公开（公告）日：2012-08-21
• [EN] NOVEL CEPHEM COMPOUNDS USEFUL FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] NOUVEAUX COMPOSÉS DE CÉPHÈME UTILES POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：FOREST LAB HOLDINGS LTD

  公开号：WO2010096798A1

  公开（公告）日：2010-08-26

  The present invention relates to new cephem compounds useful for the treatment of bacterial infections. The invention also relates to methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and to methods of treatment using the compounds. The new cephem compounds are stable, exhibit good solubility, and are particularly well suited for, e.g., parenteral administration for the treatment of bacterial infections.