61622-34-2

• 常用中文名：头孢替安
• 常用英文名：Cefotiam
• CAS号：61622-34-2
• 分子式：C₁₈H₂₃N₉O₄S₃
• 分子量：525.628
• 相关类别： 原料药 抗生素类药物 头孢菌素类药
• 发布时间：2018-02-05 08:00:00
• 更新时间：2024-01-02 17:36:49
• 用于咽喉炎、急慢性支气管炎、肺炎、乳腺炎、疖肿、丹毒、角膜溃疡、扁桃炎、膀胱炎、淋菌性尿道炎等。
   
• 对革兰阳性菌的作用与头孢唑啉相接近，而对革兰阴性菌，如嗜血杆菌、大肠杆菌、克雷白杆菌、奇异变形杆菌等作用比较优良，对肠杆菌、枸椽酸杆菌、吲哚阳性变形杆菌等也有抗菌作用。本品口服不吸收，静注本品0．5g后，当时的血药浓度为65μg／ml，半小时后为20μg／ml。肌注0．5g后半小时血药浓度达高峰为20μg／ml。本药以原形自肾排泄，t1/2约为0．5小时。在肠道中不吸收，内脏器官中药物浓度以肺中为较高，在其他内脏和肌肉组织中也有一定浓度。本品不易进入脑脊液中。临床上应用本品治疗敏感菌所致的感染如肺炎、支气管炎、胆道感染、腹膜炎、尿路感染，以及手术后或外伤引起的感染和败血症等。

名称

• 中文名: 头孢替安
• 英文名: cefotiam
• 中文别名: (6R-反式)-7-[[(2-氨基-4-噻唑基)乙酰基]氨基]-3-[[[1-[2-(二甲基氨基)乙基]-1H-四唑-5-基]硫代]甲基]-8-氧代-5-硫杂-1-氮杂二环[4.2.0]辛酸-2-烯-2-羧酸; 头孢替胺; 7-[[(2-氨基-4-噻唑基)乙酰基]氨基]-3-[[[1-[(2-(二甲氨基)乙基]-1H-四唑-5-基]硫代甲基]-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸
• 英文别名: 7-[2-(2-aminothiazol-4-yl)acetamido]-3-[1-(2-N,N-dimethylaminoethyl)-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid; MFCD00865087; CEFOTIAM HYDROCHLORIDE; Cefotiam (INN); (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-3-[[1-[2-(dimethylamino)ethyl]tetrazol-5-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Haloapor; (6R)-7t-[2-(2-amino-thiazol-4-yl)-acetylamino]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; Ceradolan; Cefotiamum [INN-Latin]; Ceradon; Cefotiamum

物化性质

• 密度: 1.8±0.1 g/cm3
• 分子式: C₁₈H₂₃N₉O₄S₃
• 分子量: 525.628
• 精确质量: 525.103516
• PSA: 251.30000
• LogP: 0.24
• 折射率: 1.855
• 储存条件: -20°C，密闭，干燥
• 水溶解性: Soluble
• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:3

  3.氢键受体数量:13

  4.可旋转化学键数量:10

  5.互变异构体数量:8

  6.拓扑分子极性表面积251

  7.重原子数量:34

  8.表面电荷:0

  9.复杂度:848

  10.同位素原子数量:0

  11.确定原子立构中心数量:2

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

生物活性

• 描述: 头孢替安是第二代头孢菌素类抗生素。头孢替安对革兰氏阳性和革兰氏阴性细菌具有广谱活性。头孢替安可有效预防各种泌尿外科手术后的感染[1][2][3]。
• 相关类别:
  研究领域 >> 感染
• 靶点:

  MIC: 1.56 μg/mL (bacterial)

• 体外研究: 头孢替安(0.78-1.65μg/mL,4-8小时)对奇异芽胞杆菌IFO 3849具有很强的抗菌活性,MIC值为1.56μg/mL[1]。细胞活力测定[1]细胞系：奇异芽胞杆菌IFO 3849浓度：0.78-1.65微克/毫升培养时间：4-8小时结果：具有较强的抗菌活性
• 体内研究: 头孢替安(50-200mg/kg；皮下注射；每天两次,共5天)可在适当剂量下在足够长的时间内治疗小鼠的奇异芽胞杆菌尿路感染[2]。动物模型：雌性CF1/b小鼠[2]剂量：50-200mg/kg给药：头孢替安(皮下注射；每天两次,共5天)。结果：治疗了实验性尿路感染。
• 参考文献:

  [1]. Yumi Hashiguchi, et al. Clinical evaluation of cefotiam in the treatment of bacteremia caused by Escherichia coli, Klebsiella species, and Proteus mirabilis: A retrospective study. J Infect Chemother. 2020 Nov;26(11):1158-1163.

  [2]. T Iwahi, et al. Comparative activities of cefotiam and cefazolin against urinary tract infections with Proteus mirabilis in mice. Antimicrob Agents Chemother

  [3]. Kazuhiro Ishizaka, et al. Randomized prospective comparison of fosfomycin and cefotiam for prevention of postoperative infection following urological surgery. J Infect Chemother. 2007 Oct;13(5):324-31.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : XI0366000 CHEMICAL NAME : 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2-amino-4-thiazolyl)acetyl) amino)-3-(((1-(2-(dimethylamino)ethyl)-1H-tetrazol-5- yl)thio)methyl)-8-oxo -, (6R-trans)- CAS REGISTRY NUMBER : 61622-34-2 LAST UPDATED : 199506 DATA ITEMS CITED : 9 MOLECULAR FORMULA : C18-H23-N9-O4-S3 MOLECULAR WEIGHT : 525.68 WISWESSER LINE NOTATION : T46 ANV ES GUTJ HVQ CMV1- ET5N CSJ BZ& G1S- ET5NNNNJ A2N1&1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7800 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,296,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3840 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 35,296,1982 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 90 gm/kg/30D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in bladder weight Blood - normocytic anemia Skin and Appendages - dermatitis, other (after systemic exposure) 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 182 gm/kg/26W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in bladder weight Skin and Appendages - dermatitis, other (after systemic exposure) Biochemical - Metabolism (Intermediary) - other proteins 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 30 gm/kg/30D-I TOXIC EFFECTS : Gastrointestinal - changes in structure or function of salivary glands Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 54600 mg/kg/26W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Skin and Appendages - dermatitis, other (after systemic exposure) Skin and Appendages - hair 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 30 gm/kg/30D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 30 gm/kg/30D-I TOXIC EFFECTS : Liver - fatty liver degeneration Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Endocrine - changes in adrenal weight 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 3),163,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 30 gm/kg/30D-I TOXIC EFFECTS : Liver - fatty liver degeneration Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Skin and Appendages - dermatitis, other (after systemic exposure) 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 3),163,1979

安全

• 危害码 (欧洲): Xi

制备

方法1：0.824g化合物(I)、0.346g 1-(2-二甲氨基乙基)-1H-四唑-5-硫醇和0.168g碳酸氢钠溶于8ml水，在65 66℃下加热1.5h。用lmol/L盐酸酸化至Ph=3后，过滤。滤液用1mol/L氢氧化钠调至Ph=5.8，用XAD-2柱层析，洗脱液为从水缓慢变为40%甲醇。收集含产物的洗脱液，冻干得0.151g头孢替安，收率14%。
其中1-(2-二甲氨基乙基)-1H-四唑-5-硫醇可由N-(2-二甲氨基乙基)异硫氰酸酯和叠氮钠在含水乙醇中加热而得。
方法2：盐酸头孢替安酯的制备。1.83g环己醇和1.45g吡啶溶于30ml二氯甲烷，在干冰冷却和搅拌下，滴加2ml氯甲酸1-氯乙基酯。加毕，在室温下搅拌16h。用饱和氯化钠水溶液洗，无水硫酸镁干燥。减压蒸去溶剂，剩余液减压蒸馏，得到无色油状的碳酸卜氯乙基酯环己基酯，收率88%，沸点100～103℃(667Pa)。
1.56g碳酸1-氯乙基酯环己基酯和5g碘化钠在50ml乙腈中，在60℃下搅拌70min。减压浓缩，剩余物用乙醚提取。提取液减压浓缩得油状的碳酸1-碘乙基酯环己基酯。
3.6g头孢替安的钾盐(CTM-K)溶于30ml二甲基甲酰胺，在冰浴冷却和搅拌下，加入得到的碳酸1-碘乙基酯环己基酯的二甲基甲酰胺溶液。搅拌5min后，将反应液倾入用冰浴冷却的150ml 20%盐水和150ml乙酸乙酯的混合液。分出有机层，用饱和盐水洗，然后用40ml 1mol/L盐酸提取。水性提取液用MCI GELCHP 20P(75～150μrn，Mitsubishi Kasei)柱层析，用0.01mol/L盐酸和乙腈-0.0lmol/L盐酸(1：4)连续洗脱。收集含产品的洗脱液，合并后减压浓缩，剩余物冻干得盐酸头孢替安酯，收率20%。