ceftriaxone sodium

• 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: ceftriaxone sodium
• 英文别名: sodium ceftriaxone；sodium;(2Z)-2-(2-amino-1,3-thiazol-4-yl)-N-[(6R,7R)-2-carboxy-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]-2-methoxyiminoethanimidate
• 化学式: C₁₈H₁₇N₈O₇S₃*Na
• 分子量: 576.57
• InChiKey: YOBPSXOHCHDCMU-VKZZUTNHSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -5.94
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  291
• 氢给体数：
  3
• 氢受体数：
  13

ADMET

毒理性

• 肝毒性

静脉注射头孢曲松与3%至46%的患者发生胆泥形成有关。儿童的发生率可能高于成人，并且与较高的剂量和较长的治疗疗程以及可能的禁食或脱水有关。该综合征被称为“伪结石病”，因为泥沙和结石主要由头孢曲松组成，停药后会自行解决，这表明可以避免手术。大多数病例发生时症状轻微或无症状。据报道，多达5%的患者出现明显的胆管炎症状。通常情况下，即使有胆绞痛，血清酶和胆红素水平也保持正常，但在罕见情况下，会出现胆汁淤积性黄疸或胆石性胰腺炎，这可能是严重的，需要手术治疗。胆泥和胆囊疾病的症状可能在开始治疗后的几天内出现，但通常在停用头孢曲松后迅速解决，尽管泥沙和胆结石可能通过超声检测几个月。

Parenteral administration of ceftriaxone has been associated with development of biliary sludge in 3% to 46% of patients. The incidence may be higher in children than adults and is associated with higher doses and longer courses of treatment and possibly with fasting or dehydration. The syndrome is referred to as “pseudo-lithiasis” as the sludge and stones consist largely of ceftriaxone and they resolve spontaneously when the drug is stopped, indicating that surgery can be avoided. Most cases occur with minimal or no symptoms. Frank symptoms of cholecystitis are reported in up to 5% of patients who develop pseudo-lithiasis. Typically, serum enzymes and bilirubin levels remain normal even with biliary colic, but in rare instances there is cholestatic jaundice or gallstone pancreatitis that can be severe and require surgical intervention. Sludge and symptoms of gallbladder disease can arise within a few days of starting therapy, but typically resolve rapidly once ceftriaxone is stopped, although sludge and gallstones may be detectable by ultrasound for several months.

来源:LiverTox

反应信息

• 作为反应物：
  描述：

  ceftriaxone sodium 、 tin(ll) chloride 在 水 作用下， 反应 6.0h， 以75%的产率得到
  参考文献：
  名称：

  Cephalosporin Tin(II) Complexes: Synthesis, Characterization, and Antibacterial Activity

  摘要：

  The synthesis and spectral characterization of mononuclear cephalosporin tin(II) complexes of general formula [Sn(L)Cl] (L = monoanion of cephalothin HL1, cephradine HL2, cefotaxime HL3, cefazolin HL4, and ceftriaxone HL5), are reported. They were characterized by physicochemical and spectroscopic methods. The spectra indicated that the antibiotics act as multidentate ligand toward metal ions, via the amide and lactam carbonyl and carboxylate and N-azomoieties. The complexes are nontoxic, insoluble in water, and common organic solvents and probably have polymeric structures. The ligands and their tin complexes have been screened for their antibacterial activities and found to be quite active in this respect. Coordination of cephalothin and cephradine to tin(II) ion showed an enhancement of the antibacterial activity.

  DOI：

  10.1080/15533174.2012.680164
• 作为产物：
  描述：

  头孢曲松 在 sodium acetate 、 三乙胺 作用下， 以 水 、 丙酮 为溶剂， 生成 ceftriaxone sodium
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF CEPHALOSPORIN ANTIBIOTIC
  [FR] PROCEDE DE PREPARATION D'UN ANTIBIOTIQUE A BASE DE CEPHALOSPORINE

  摘要：

  一种制备头孢菌素抗生素的方法，其中公式（I）中R1代表氢、三苯甲基等；R3是羧酸盐离子或COORd，其中Rd代表氢、酯或形成盐的反离子；R4代表H、OCH3、OCOCH3、=CH2、OCONH2等，包括以下步骤：（i）在溶剂存在下，在温度范围为-50℃至+50℃的条件下，将公式（III）的活性衍生物（其中X代表卤素原子）与公式（XV）的7-氨基头孢菌素衍生物（其中R代表氢、较低的烷基等）缩合，以产生公式（XVI）的化合物；（ii）使用无机碱维持pH在5.0-10.0范围内；（iii）使用硫脲将公式（XVI）的化合物环化，以产生公式（I）的化合物。

  公开号：

  WO2005019227A1

文献信息

• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• Process for the preparation of cephalosporin intermediate and its use for the manufacture of cephalosporin compounds
  申请人：Orchid Chemicals and Pharmaceuticals Limited

  公开号：US20030199712A1

  公开（公告）日：2003-10-23

  The present invention relates to a process for the preparation of 4-halogeno-2-substitutedimino-3-oxo-butyric acid of formula (I) 1 wherein R 1 represents CH 3 , CR a R b COOR c where R a and R b independently represent hydrogen or methyl and R c represents hydrogen or (C 1 -C 6 )alkyl, X represents halogen such as chlorine or bromine, also discloses the activation of this acid and its further use in the preparation of cephalosporanic antibiotics (II) in excellent yields and purity

  本发明涉及一种制备式(I)的4-卤代-2-取代亚胺-3-氧代丁酸的方法，其中R1代表CH3，CRaRbCOORc，其中Ra和Rb独立地代表氢或甲基，Rc代表氢或(C1-C6)烷基，X代表卤素如氯或溴，同时还揭示了该酸的活化以及其在制备头孢菌素类抗生素(II)中的进一步应用，产率高，纯度高。
• 8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents
  申请人：Bradbury J. Barton

  公开号：US20060173026A1

  公开（公告）日：2006-08-03

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A 1 , A 8 , R 2 , R 3 , R 5 , R 6 , R 7 , and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of compounds of Formula I and/or Formula II and one or more other active agents. The invention also provides methods for treating microbial and protozoal infections in animals.

  该发明提供了具有抗微生物活性的化合物和盐，其化学结构分别为公式I和公式II。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。变量A1，A8，R2，R3，R5，R6，R7和R9在此处有定义。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和选择性抑制剂。该发明还提供了包含公式I或公式II化合物以及一个或多个载体、赋形剂或稀释剂的抗微生物组合物，包括制药组合物。这些组合物可以含有公式I或公式II化合物作为唯一活性剂，也可以含有公式I和/或公式II化合物以及一个或多个其他活性剂的组合。该发明还提供了治疗动物微生物和原虫感染的方法。
• [EN] MODULATION OF IMMUNE RESPONSES BY ADMINISTRATION OF ROXITHROMYCIN OR ITS DERIVATIVE<br/>[FR] MODULATION DES RÉPONSES IMMUNES PAR ADMINISTRATION DE ROXITHROMYCINE OU DE SES DÉRIVÉS
  申请人：Y S THERAPEUTICS CO LTD

  公开号：WO2009023196A1

  公开（公告）日：2009-02-19

  Provided are compounds of formula (III) useful for modulation of immune responses, compositions comprising the compounds, and methods of use of such compositions for treating diseases or disorders involving an immune response. In certain embodiments, the compounds are useful for the treatment of diseases or disorders associated with transendothelial migration of T cells and activated T cells, and proinflammatory cytokine production from T cells and macrophages. Diseases or disorders that can be treated include arthritic and rheumatic disorders, such as rheumatoid arthritis.

  提供的是化合物的公式（III），用于调节免疫反应，包含这些化合物的组合物，以及使用这些组合物治疗涉及免疫反应的疾病或紊乱的方法。在某些实施例中，这些化合物可用于治疗与T细胞和活化T细胞的经内皮迁移以及T细胞和巨噬细胞的促炎细胞因子产生相关的疾病或紊乱。可以治疗的疾病或紊乱包括关节炎和风湿性疾病，如类风湿性关节炎。
• 8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents
  申请人：Bradbury J. Barton

  公开号：US20060100215A1

  公开（公告）日：2006-05-11

  The invention provides compounds and salts of Formula I and Formula II: which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables n, m, p, R A , R B , A 1 , R 2 , R 3 , R 5 , R 6 , R 7 , A 8 and R 9 are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and/or selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in eukaryotes.

  该发明提供了化合物和盐的公式I和公式II：具有抗微生物活性。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。这里定义了变量n、m、p、RA、RB、A1、R2、R3、R5、R6、R7、A8和R9。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和/或选择性抑制剂。该发明还提供了抗微生物组合物，包括含有一个或多个公式I或公式II化合物和一个或多个载体、赋形剂或稀释剂的制药组合物。这些组合物可能仅含有公式I或公式II化合物作为唯一活性剂，也可能含有公式I或公式II化合物与一个或多个其他活性剂的组合。该发明还提供了治疗真核生物微生物感染的方法。