7-{[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino}-3-{[(2-furanylcarbonyl)-thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | 1219533-13-7

• 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: 7-{[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino}-3-{[(2-furanylcarbonyl)-thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• 英文别名: 7-{[(2-amino-4-thiazolyl)(methoxyimino)ethanoyl]amino}-3-{[(2-furylcarbonyl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid；ceftiofur hydrochloride；· Ceftiofur；zinc ceftiofur；7-[[2-(2-Amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 1219533-13-7
• 化学式: C₁₉H₁₇N₅O₇S₃
• 分子量: 523.571
• InChiKey: ZBHXIWJRIFEVQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  256
• 氢给体数：
  3
• 氢受体数：
  13

ADMET

代谢

对4只雄性和4只雌性Sprague-Dawley大鼠肌肉注射(14)C-头孢噻呋（2毫克/千克体重）的研究发现，给药剂量的55%通过尿液排出，大约30%通过胃肠道和粪便排出。主要的尿液代谢物是脱氧酰头孢噻呋（DFC）。头孢噻呋的代谢在通过肌肉注射途径给予(14)C-头孢噻呋（2毫克/千克体重）的小牛中相似。未代谢的头孢噻呋也存在于尿液中（总放射活性的4.4-21%）。

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and faeces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).

来源:Hazardous Substances Data Bank (HSDB)

代谢

在一项与牛进行的比较研究中，一组Sprague-Dawley大鼠（每性别7只）接受了单次口服剂量的(14)C-头孢噻呋（200 mg/kg体重）。大约55%的总剂量在尿液中回收，其余部分存在于粪便和胃肠道中。...主要的尿液代谢物是头孢噻呋砜胱氨酸硫酯。

A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. ... The major urinary metabolite was ceftiofursulfoxide cysteine thioester.

来源:Hazardous Substances Data Bank (HSDB)

代谢

高效液相色谱分析体外由aro氯诱导的大鼠肝脏S-9部分形成的(14)C-头孢噻呋代谢物显示，脱氧头孢噻呋是主要的代谢物。低剂量(119 mg/kg bw)的头孢噻呋在15分钟内被完全代谢。较高剂量(857 mg/kg bw)在孵化60分钟后转化为脱氧头孢噻呋。

HPLC analysis of metabolites of (14)C-ceftiofur formed by arochlor-induced rat liver S-9 fractions in vitro revealed that desfuroylceftiofur was the major metabolite. Low doses (119 mg/kg bw) of ceftiofur were completely metabolized within 15 minutes. Higher doses (857 mg/kg bw) were converted to desfuroylceftiofur after 60 minutes of incubation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在8周大的Sprague-Dawley大鼠（每性7只）中，通过口服灌胃给予（14）C-头孢噻呋（800 mg/kg体重/天），连续5天的研究发现了几个尿液代谢物，包括去戊酰头孢噻呋、头孢噻呋亚砜和胱氨酸二硫。

A study in 8-week old Sprague-Dawley rats (7/sex) treated with (14)C-ceftiofur (800 mg/kg bw/day) by oral gavage for 5 days revealed several urinary metabolites, including desfuroylceftiofur, ceftiofur sulfoxide, and cysteine disulfide.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有需要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预见癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的呕吐反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%盐水（NS）或乳酸林格液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。使用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/ 在一项吸入研究中，将头孢喹夫以8.3毫克/升的气溶胶浓度给予5只雄性和5只雌性Sprague-Dawley大鼠，暴露时间为4小时。在暴露期间，大鼠表现出流涎、鼻涕和呼吸困难；这些症状在暴露后1小时内几乎消失。暴露后的症状包括6只大鼠出现腹泻，1只大鼠鼻孔周围有红色结痂物质。大体和显微镜检查没有发现任何与治疗相关的变化。[联合国粮农组织/世界卫生组织食品添加剂专家委员会；世界卫生组织食品添加剂系列36：某些兽药残留食品中毒理学评估：头孢喹夫（1996年）。截至2006年7月17日，可从以下网址获得：http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ In an inhalation study, ceftiofur was administered at an aerosol concentration of 8.3 mg/L to a group of 5 male and 5 female Sprague-Dawley rats for a 4-hr exposure period. During exposure, rats exhibited salivation, nasal discharge and dyspnea; these signs virtually disappeared within 1 hr after exposure. Post-exposure signs included diarrhea in 6 rats, and 1 rat exhibited a red encrusted material around the nares. Both gross and microscopic examination did not reveal any treatment-related changes.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/在急性口服研究中，将头孢噻呋以单次剂量最高7800毫克/千克体重给药给Sprague-Dawley大鼠（每组10只/性别）。在两个最高剂量水平上观察到与治疗相关的腹泻。没有观察到其他与治疗相关的体征。[联合国粮农组织/世界卫生组织食品添加剂专家联合委员会；世界卫生组织食品添加剂系列36：某些兽药残留食品中毒理学的评估：头孢噻呋（1996年）。截至2006年7月17日，可从以下网址获得：http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

/LABORATORY ANIMALS: Acute Exposure/ In an acute oral study, ceftiofur was administered as a single dose of up to 7800 mg/kg bw to groups of Sprague-Dawley rats (10/sex). Treatment-related diarrhea was noted at the 2 highest dose levels. No other treatment-related signs were observed.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/ 在对牛每天肌肉注射高达55毫克/千克体重，连续5天，以及对猪每天肌肉注射高达125毫克/千克体重，连续5天的研究中，最显著的发现是短暂的注射部位反应。[欧洲药品管理局（EMA），欧洲药品评估机构，兽药评估单位，兽药产品委员会；头孢噻呋，摘要报告（2）。EMA/MRL/498/98-最终（1999年7月）。截至2006年7月21日，可从以下网址获得：http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

/LABORATORY ANIMALS: Acute Exposure/ In studies in which cattle were given daily intramuscular injections of up to 55 mg/kg bw/day for 5 days and pigs were given dally intramuscular injections of up to 125 mg/kg bw/day for 5 days, transient injection site reactions were the most notable findings.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Ceftiofur, Summary Report (2). EMEA/MRL/498/98-Final (July 1999). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

对4只雄性和4只雌性Sprague-Dawley大鼠肌肉注射(14)C-头孢噻呋（2毫克/千克体重）的研究发现，给药剂量的55%通过尿液排出，大约30%通过消化道和粪便排出。主要的尿液代谢物是脱氧酰头孢噻呋（DFC）。头孢噻呋在通过肌肉注射途径给予(14)C-头孢噻呋（2毫克/千克体重）的犊牛中的代谢情况相似。未代谢的头孢噻呋也出现在尿液中（总放射活性的4.4-21%）。

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and feces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项与牛的比较研究中，一组Sprague-Dawley大鼠（每性别7只）接受了单次口服剂量的(14)C-头孢噻呋（200 mg/kg体重）。大约55%的总剂量在尿液中回收，其余存在于粪便和胃肠道中。6小时时的血浆浓度为1 mg/kg，所有组织中都有微量的头孢噻呋存在（即肝脏、肌肉和脂肪）。肾脏中的残留水平最高，为0.7 mg/kg。

A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. Plasma concentration at 6 hr was 1 mg/kg and trace amounts of ceftiofur were present in all tissues (i.e. liver, muscle and fat). The highest residue levels (0.7 mg/kg) were present in kidney.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

对泌乳期奶牛使用(14)C-头孢噻呋（2.3 mg/kg 体重/天，连续5天）进行研究，结果显示32-38%的放射性物质以自由代谢物的形式存在于牛奶中。主要的代谢物是脱脲基头孢噻呋半胱氨酸二硫化物，占总放射性的7-9%。牛奶中没有检测到母体化合物。

A study of lactating cows treated with (14)C-ceftiofur (2.3 mg/kg bw/day for 5 days) revealed that 32-38% of the radioactivity was present in the milk as free metabolites. The major metabolite was desfuroylceftiofur cysteine disulfide representing 7-9% of the total radioactivity. No parent compound was detected in the milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项对公牛进行的研究中，通过静脉注射(14)C-头孢噻呋，发现大约55%的给药剂量通过尿液排出，大约30%通过胃肠道和粪便排出。在尿液和血浆中，最初的代谢物是去氧甲酰头孢噻呋。放射性代谢物的HPLC分析结果与在大鼠研究中发现的结果相似。产生了一系列代谢物，主要代谢物（占尿液代谢物总量的87%）是去氧甲酰头孢噻呋酰胺结合物。在尿液中没有观察到母化合物。

A study of im administration of (14)C-ceftiofur in a bull revealed that 55% of the administered dose was excreted in the urine and approximately 30% in the GI tract and feces. The initial metabolite in both urine and plasma was desfuroylceftiofur. HPLC analysis of radioactive metabolites was similar to the results found in the rat studies. A number of metabolites were produced, the major metabolite (87% of total urinary metabolites) being desfuroylceftiofur acetamide conjugates. No parent compound was observed in the urine.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  7-{[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino}-3-{[(2-furanylcarbonyl)-thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 在 sodium acetate 、 sodium chloride 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 ceftiofur sodium
  参考文献：
  名称：

  WO2007/42917

  摘要：

  公开号：
• 作为产物：
  描述：

  7-amino-3-[(2-furanylcarbonyl)thiomethyl]-3-cephem-4-carboxylic acid 、 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetylchloride 在 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 7-{[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino}-3-{[(2-furanylcarbonyl)-thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  WO2007/42917

  摘要：

  公开号：

文献信息

• Characterization and engineering of cephalosporin C acylases to produce 7-Aminocephalosporanic acid
  作者：Xiangying Li、Jingang Wang、Wencheng Su、Congcong Li、Ge Qu、Bo Yuan、Zhoutong Sun

  DOI：10.1016/j.mcat.2023.113595

  日期：2023.11

  8-fold increase in specific enzymatic activity (6.1 U/mg) was obtained compared to the wild-type enzyme. The engineered variant also enabled the hydrolysis of a variety of β-lactam antibiotics including Penicillin G and phenylacetyl-7-aminodeacetoxycephalosporanic acid (G-7-ADCA). Overall, this study discovered new CCAs from distinct bacterial origins and enabled the synthesis of various core β-lactam

  7-氨基头孢烷酸(7-ACA)是合成β-内酰胺类抗生素的核心核。头孢菌素 C 酰化酶 (CCA) 是一类能够将头孢菌素 C (CPC) 水解为 7-ACA 的酶。在这项研究中，我们鉴定、表征并设计了新的 CCA 来制备 7-ACA。使用组合活性位点饱和测试（CAST）和迭代进化进行多轮半理性酶设计后获得最佳突变体A14（L159S/A419V）。与野生型酶相比，酶比活性增加了 2.8 倍（6.1 U/mg）。该工程变体还能够水解多种 β-内酰胺抗生素，包括青霉素 G 和苯乙酰基-7-氨基脱乙酰氧基头孢菌酸 (G-7-ADCA)。全面的，
• Use of antibiotics as vaccine adjuvants
  申请人：Ohara K. Michael

  公开号：US20070141086A1

  公开（公告）日：2007-06-21

  The invention describes an adjuvant composition comprising an antimicrobial agent, in particular an azalide, wherein the antimicrobial agent acts as an adjuvant. More particularly, the adjuvant composition is a vaccine adjuvant. The invention further describes a vaccine comprising several components comprising (a) at least one antigen and (b) at least one antimicrobial agent, in particular an azalide, wherein the azalide acts as an adjuvant. An adjuvant composition or vaccine of the present invention is useful in the prevention and treatment of diseases caused by a pathogenic agent, a cancerous cell, or an allergen.
• METHOD OF ADMINISTERING AN INJECTABLE ANTIBIOTIC TO AN ANIMAL
  申请人：Brown Scott A.

  公开号：US20110098266A1

  公开（公告）日：2011-04-28

  A method of administering an antibiotic to an animal in need thereof, including the step of injecting the antibiotic subcutaneously at the junction of a pinna with the cranium of the animal, is disclosed.
• US8968759B2
  申请人：——

  公开号：US8968759B2

  公开（公告）日：2015-03-03
• WO2007/42917
  申请人：——

  公开号：——

  公开（公告）日：——