55268-75-2

• 常用中文名：头孢呋肟
• 常用英文名：Cefuroxime
• CAS号：55268-75-2
• 分子式：C₁₆H₁₆N₄O₈S
• 分子量：424.385
• 相关类别： 原料药 抗生素类药物 头孢菌素类药
• 发布时间：2018-06-20 17:34:29
• 更新时间：2024-01-02 15:08:02
• Cefuroxime 是一种具有口服活性的第二代头孢菌素抗生素 (antibiotic),增加了对乳酸酶 (β-lactamase) 的稳定性。Cefuroxime 具有广谱的抑制活性,对革兰氏阳性菌和革兰氏阴性菌都有效。

名称

• 中文名: 头孢呋辛
• 英文名: cefuroxime
• 中文别名: 头孢呋肟; 头孢呋辛酯杂质 D; 头孢呋辛酸
• 英文别名: EINECS 259-560-1; cefuroxim; U1troxim; Ketocef; (6R,7R)-3-[(carbamoyloxy)methyl]-7-{[(2Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Cefuroxime; Biocidin; cefaloxime; 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-[[(aminocarbonyl)oxy]methyl]-7-[[(2Z)-2-(2-furanyl)-2-(methoxyimino)-1-oxoethyl]amino]-8-oxo-, (6R,7R)-; Cephuroxime; MFCD00864991; CXM; Biofuroksym; (6R,7R)-3-[(Carbamoyloxy)methyl]-7-{[(2Z)-2-(2-furyl)-2-(methoxyimino)acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-3-Carbamoyloxymethyl-7-[2-(2-furyl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid; EkLxirrm

物化性质

• 密度: 1.8±0.1 g/cm3
• 熔点: 171.5-173°C
• 分子式: C₁₆H₁₆N₄O₈S
• 分子量: 424.385
• 精确质量: 424.068878
• PSA: 199.06000
• LogP: 0.47
• 外观性状: 白色结晶，[α]召+63.7°(C=1.0，0.2mol/L磷酸盐缓冲液pH=7)。UV最大吸收(pH=6磷酸缓冲液)：274nm(ε17600)。头孢呋辛钠(Cefuroxime Sodium)：C16H15N4aO8SNa。[56238-63-2]。白色固体，易溶于水或缓冲溶液，溶于甲醇，极微溶于乙醇乙酯、乙醚、辛醇、苯或氯仿，水中溶解度为500mg/2.5ml。pKa(水)：2.5；pKa(Z.甲基甲酰胺)：5.1。[α]D20 +60°(C=0.91，水)。
• 折射率: 1.735
• 储存条件: 2-8°C，干燥
• 分子结构:

  1、 摩尔折射率：96.66

  2、 摩尔体积（cm³/mol）：241.0

  3、 等张比容（90.2K）：716.3

  4、 表面张力（dyne/cm）：78.0

  5、 极化率（10-24cm3）：38.32

• 更多:

  1.性状：白色至淡黄色的粉末，略有异臭，味苦。

  2.溶解性：易溶于水或缓冲溶液，溶于甲醇，极微溶于乙醇乙酯、乙醚、辛醇、苯或氯仿

生物活性

• 描述: Cefuroxime 是一种具有口服活性的第二代头孢菌素抗生素 (antibiotic),增加了对乳酸酶 (β-lactamase) 的稳定性。Cefuroxime 具有广谱的抑制活性,对革兰氏阳性菌和革兰氏阴性菌都有效。
• 相关类别:
  研究领域 >> 感染
  信号通路 >> 抗感染 >> 细菌
• 体外研究: 头孢呋辛对金黄色葡萄球菌(MIC=0.25μg/ml)具有很高的活性,无论菌株是否产生青霉素酶。对甲氧西林敏感的金黄色葡萄球菌、耐甲氧西林的金黄色葡萄球菌、化脓性链球菌、肺炎链球菌、绿色链球菌、粪链球菌和梭状芽孢杆菌的MIC值分别为0.25μg/ml、5.9μg/ml、0.125μg/ml、0.125μg/ml、0.125μg/ml、>125.0μg/ml和1.2μg/ml[1]。头孢呋辛(10-100μg/ml；2-6小时)杀菌迅速,对金黄色葡萄球菌的作用相对较慢,但即使如此,6小时内99%以上的初始接种物被杀死,革兰氏阴性菌被迅速杀死,大多数情况下99%以上的超大接种物在2小时内被杀死；产β-内酰胺酶菌株与非产酶菌株一样被杀死[1]。
• 体内研究: 家兔(体重2.0～2.5kg)静脉注射金黄色葡萄球菌630株(青霉素酶产生菌),经保护试验,头孢呋辛的中位有效剂量为3mg/kg。
• 参考文献:

  [1]. Callaghan, et al. Cefuroxime, a New Cephalosporin Antibiotic: Activity in Vitro. Antimicrob Agents Chemother. 1976 Mar;9(3):511-9.

  [2]. D M Ryan, et al. Cefuroxime, a New Cephalosporin Antibiotic: Activity in Vivo. Antimicrob Agents Chemother. 1976 Mar;9(3):520-5.

毒性和生态

毒理学数据: 口服-大鼠 LD50: 10000 毫克/公斤; 静脉-小鼠 LD50: 10400 毫克/公斤 CHEMICAL IDENTIFICATION RTECS NUMBER : XI0329000 CHEMICAL NAME : 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 3-(((aminocarbonyl)oxy)methyl)-7-((2- furanyl(methyoxyimino)acetyl)amino)-8-oxo-, (6R-(6-alpha,7-beta(Z)))- CAS REGISTRY NUMBER : 55268-75-2 LAST UPDATED : 199707 DATA ITEMS CITED : 19 MOLECULAR FORMULA : C16-H16-N4-O8-S MOLECULAR WEIGHT : 424.42 WISWESSER LINE NOTATION : T46 ANV ES GUTJ G1OVZ HVQ CMVYUNO1&- BT5OJ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 64 mg/kg/16H-I TOXIC EFFECTS : Behavioral - toxic psychosis REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,965,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >8 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 10400 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRUGAY Drugs. International Journal of Current Therapeutics and Applied Pharmacology Reviews. (ADIS Press International Inc., Suite B-30, Oxford Ct. Business Center, 582 Middletown Blvd., Langhorne, PA 19047) V.1- 1971- Volume(issue)/page/year: 17,233,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >1500 mg/kg TOXIC EFFECTS : Behavioral - food intake (animal) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - hypermotility, diarrhea REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >300 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),124,1979 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 30 gm/kg/5W-I TOXIC EFFECTS : Lungs, Thorax, or Respiration - changes in lung weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood - changes in erythrocyte (RBC) count REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),130,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 45 gm/kg/5W-I TOXIC EFFECTS : Liver - changes in liver weight Blood - normocytic anemia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),130,1979 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 8800 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - other postnatal measures or effects REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),245,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 24 gm/kg SEX/DURATION : male 60 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),245,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 32 gm/kg SEX/DURATION : male 9 week(s) pre-mating female 2 week(s) pre-mating female 1-7 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),245,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 4400 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) REFERENCE : NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 27(Suppl 6),245,1979

安全

• 个人防护装备: Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
• 危害码 (欧洲): Xn
• 风险声明 (欧洲): R42/43
• 安全声明 (欧洲): 22-24-37-45
• 危险品运输编码: NONH for all modes of transport
• RTECS号: XI0329000

合成路线

1189-71-5 56271-94-4 ~92% 55268-75-2

文献：Antibioticos S.p.A. Patent: US6642378 B1, 2003 ; Location in patent: Page/Page column 2-3 ;

870-30-4 56271-94-4 ~71% 55268-75-2

文献：Antibioticos S.p.A. Patent: US6642378 B1, 2003 ; Location in patent: Page/Page column 3-4 ;

97232-97-8 ~% 55268-75-2

文献：Journal of Pharmaceutical Sciences, , vol. 83, # 4 p. 553 - 558

上下游产品

上游产品  4
1189-71-5 56271-94-4 870-30-4 97232-97-8
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制备

方法1：以头孢噻吩钠(Ⅰ)为原料，用酶进行水解脱去3位侧链上的乙酰基，再先后和二苯基偶氮甲烷及三氯乙酰基异氰酸酯反应，对羧基和醇进行保护，得化合物(Ⅱ)。化合物(Ⅱ)用五氯化磷进行处理，使7位侧链断裂，得化合物(Ⅲ)。化合物(Ⅲ)先用弱碱的甲醇溶液，再用强酸水解，脱去保护基，得化合物(Ⅳ)。化合物(Ⅳ)和侧链反应可得头孢呋辛。头孢呋辛和2-乙基己酸钠作用，可得头孢呋辛钠。

其中侧链的制备及和化合物(Ⅳ)的反应可进行如下。在0℃和搅拌下，往14.99g(0.072mol)五氯化磷悬浮于150ml干燥的二氯甲烷溶液中，加入27.5mlN,N-二甲基甲酰胺。冷却至-10℃，再加入12.17g(0.072mol)2-(呋喃-2-基)-2-甲氧亚氨基乙酸(Ⅸ)。在－10℃，继续搅拌反应15min后，加入35g碎冰在0继续搅拌10min后，分出下层的二氯甲烷层，留待后用。

75mlN,N-二甲基甲酰胺、75ml乙腈、42ml三乙胺和(6R,7R)-7-氨基-3-[(氨甲酰氧基)甲基]头孢-3-烯-4-羧酸混合，搅拌下浸入冰浴中，再加入10ml水。在0～2℃下搅拌45mol，直到固体全部溶解，形成黄色的溶液。然后在10min内，－10℃和搅拌下，往该黄色溶液中加入上面制得的二氯甲烷溶液，此时温度会缓慢升至0℃。接着在0～2℃下继续反应1g。移去冷浴，让其在1g内自然升温至20℃。在5℃下，把该反应液慢慢加入100ml的2mol／L盐酸和1.15L的冷水所成的溶液中。用2mol/L盐酸（约10ml）调节，使该二相混合液的PH值在2以下，继续搅拌，并再冷却至5℃。析出沉淀，过滤，用100ml二氯甲烷和250ml水洗，于40℃真空干燥过夜，得22.04g头孢呋辛，收率86.6％。