127045-41-4

• 常用中文名：帕珠沙星
• 常用英文名：Pazufloxacin
• CAS号：127045-41-4
• 分子式：C₁₆H₁₅FN₂O₄
• 分子量：318.300
• 相关类别： 原料药 人工合成抗感染类药 喹诺酮类药
• 发布时间：2018-03-24 08:00:00
• 更新时间：2025-08-20 09:30:57
• 【用途一】
  本品是国家二类新药甲磺酸帕珠沙星的关键中间体，也即碱基料，是分子结构中的主体部分，只需与甲磺酸成盐即得原料药。
  【用途二】
  用于治疗急慢性肺炎、呼吸道感染等病症
  【用途三】
  仍在临床试验中。
  【用途四】
  本品属于第三代喹诺酮类抗菌药。

名称

• 中文名: 帕珠沙星
• 英文名: Pazufloxacin
• 中文别名: (S)-(-)-10-(1-氨基环丙基)-9-氟-3-甲基-7-氧代-2,3-二氢-7H-吡啶并[1,2,3-DE][1,4]苯并恶嗪-6-羧酸甲磺酸盐; 帕苏沙星
• 英文别名: T-3761; 7H-1,4-Oxazino[2,3,4-ij]quinoline-6-carboxylic acid, 10-(1-aminocyclopropyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-, (3S)-; PAZUFLOXAXIN; MFCD00865012; (-)-(3S)-10-(1-Aminocyclopropyl)-9-fluoro-2,3-dihydro-3-methyl-7--oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid; T666 1A M BN EO KVT&&J C1 HF LVQ G- AL3TJ AZ &&S Form; (3S)-10-(1-Aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid; ALKALYL; (S)-10-(1-Aminocyclopropyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7h-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid; Pazufloxaxin mesilate; Pazufloxacin318.3; Pazufloxacin

物化性质

• 密度: 1.6±0.1 g/cm3
• 沸点: 531.5±50.0 °C at 760 mmHg
• 熔点: 269-271°C
• 分子式: C₁₆H₁₅FN₂O₄
• 分子量: 318.300
• 闪点: 275.2±30.1 °C
• 精确质量: 318.101593
• PSA: 94.55000
• LogP: 0.09
• 外观性状: 白色至淡,黄色结晶
• 蒸汽压: 0.0±1.5 mmHg at 25°C
• 折射率: 1.692
• 储存条件: 2-8°C
• 稳定性:

  盐酸帕楚沙星(Pazufloxacin Hydrochloride)：C16H15FN2O4?HCl。熔点243.5-247.5℃。[α]_D²³-32.5°(C=0.5，水)。; 甲磺酸帕楚沙星(Pazufloxacin Methanesulformte)：C16H15FN2O4?CH3SO3H。[163680-77-1]。无色棱状结晶，熔点258～259℃(分解)。[α]_D²⁰-64.2°(C=1，1.0mol/L氢氧化钠溶液)。25℃时水中溶解度＞200mg/ml。

• 分子结构:

  1、 摩尔折射率：77.70

  2、 摩尔体积（cm³/mol）：202.8

  3、 等张比容（90.2K）：599.7

  4、 表面张力（dyne/cm）：76.4

  5、 极化率（10-24cm3）：30.80

• 计算化学:

  1.疏水参数计算参考值（XlogP）:-0.8

  2.氢键供体数量:2

  3.氢键受体数量:7

  4.可旋转化学键数量:2

  5.互变异构体数量:无

  6.拓扑分子极性表面积92.9

  7.重原子数量:23

  8.表面电荷:0

  9.复杂度:603

  10.同位素原子数量:0

  11.确定原子立构中心数量:1

  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

• 更多:

  1.性状：棱状无色结晶。

  2.熔点：259-259℃。

  3.比旋光度：[α]_D²⁵-88.0°(C=0.5，0.05mol/L氢氧化钠溶液)。

生物活性

• 描述: Pazufloxacin (T-3761)是氟喹诺酮类广谱抗生素。
• 相关类别:
  信号通路 >> 抗感染 >> 细菌
  研究领域 >> 感染
• 参考文献:

  [1]. Fukuoka, Y., et al., In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative. Antimicrob Agents Chemother, 1993. 37(3): p. 384-92.

  [2]. Muratani, T., M. Inoue, and S. Mitsuhashi, In vitro activity of T-3761, a new fluoroquinolone. Antimicrob Agents Chemother, 1992. 36(10): p. 2293-303.

毒性和生态

毒理学数据: 急性毒性LD50雄小鼠(mg/kg)：＞500静脉注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : UU8815300 CHEMICAL NAME : 7H-Pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid, 2,3-dihydro-10-(1-aminocyclopropyl)-9- fluoro-3-methyl-7-oxo-, (S)- CAS REGISTRY NUMBER : 127045-41-4 LAST UPDATED : 199801 DATA ITEMS CITED : 14 MOLECULAR FORMULA : C16-H15-F-N2-O4 MOLECULAR WEIGHT : 318.33 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 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: 43(Suppl 2),132,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) 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: 48,754,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 341 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea 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: 48,754,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/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: 48,754,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) 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: 48,754,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 783 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Skin and Appendages - dermatitis, other (after systemic exposure) 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: 48,754,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/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: 48,754,1995 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 400 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease 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: 48,754,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 36400 mg/kg/13W-I TOXIC EFFECTS : Gastrointestinal - other changes Musculoskeletal - joints 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: 48,790,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 16800 mg/kg/4W-I TOXIC EFFECTS : 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: 43(Suppl 2),132,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2730 mg/kg/13W-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Musculoskeletal - joints 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: 48,790,1995 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 125 gm/kg SEX/DURATION : male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 48,832,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 16500 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system 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: 48,832,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 39 gm/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - other effects 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: 48,832,1995

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302-H312-H332
• 警示性声明: P280
• 个人防护装备: dust mask type N95 (US);Eyeshields;Gloves
• 危害码 (欧洲): Xn: Harmful;
• 风险声明 (欧洲): R20/21/22
• 安全声明 (欧洲): S36/37
• 危险品运输编码: NONH for all modes of transport
• RTECS号: UU8815300

制备

【方法一】
2，3，4，5-四氟苯甲酸乙酯与丙二酸二叔丁酯反应，然后与三氟乙酸经脱羧反应得4-羧甲基-2，3，5-三氟苯甲酸乙酯，用二苯基重氮甲烷酯化。在甲醇钠存在下用聚甲醛处理，在侧链的活性亚甲基处生成羟甲基，再处理成亚甲基。和三甲基硫氧碘化物反应后，引入环丙基，选择性水解成4-(1-羰基环丙基)-2，3，5-三氟苯甲酸乙酯。与氯代甲酸乙酯和叠氮化钠反应，然后用苄醇酯化，再选择性水解得4-[1-(苯甲酰基羰氨基)环丙基]-2，3，5-三氟苯甲酸。和乙氧羰基醋酸镁及1，1L羰基二咪唑反应，使侧链甲酸基转化为甲酰基醋酸乙酯，与N，N-二甲基甲酰胺缩二甲醇和(S)-氨基-1-丙醇缩合后，再环合得2，3-二氢-7H-吡啶并[1，2，3-de][1，4]苯并恶嗪的母环，最后水解、氢化得T-3761的盐酸盐，中和得帕楚沙星。
帕楚沙星(1.00g，3.14mmo1)悬浮于10ml乙醇中，在50℃和搅拌下加入甲磺酸(0.31g，3.22mmo1)，然后冷至室温。过滤收集沉淀，即得1.22g甲磺酸帕楚沙星，收率94%。