89786-04-9

• 常用中文名：三唑巴坦
• 常用英文名：Tazobactam
• CAS号：89786-04-9
• 分子式：C₁₀H₁₂N₄O₅S
• 分子量：300.291
• 相关类别： 原料药 抗生素类药物 β-内酰胺酶抑制剂
• 发布时间：2018-03-13 08:00:00
• 更新时间：2025-08-25 22:41:27
• Tazobactam是一种β-内酰胺酶抑制剂, 具有抗菌活性。

名称

• 中文名: 他唑巴坦
• 英文名: tazobactam
• 中文别名: 2α-甲基-2β-(1,2,3-三氮唑-1-基)甲基青霉烷砜-3α-羧酸; 三唑巴坦; 三唑烷砜
• 英文别名: MFCD00867002; YTR 830H; Tazobactam; [2S-(2a,3b,5a)]-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide; 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-, 4,4-dioxide, (2S,3S,5R)-; T45 ANV ESWTJ F1 GVQ F1- AT5NNNJ &&(2S,3S,5R)- Form; (2S,3S,5R)-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 4,4-dioxide; UNII-SE10G96M8W; TAZOBACTANACID; YTR-830H; 2b-[(1,2,3-triazol-1-yl)methyl]-2a-methylpenam-3a-carboxylic acid 1,1-dioxide; Tazobactan acid; 2-METHANESULFONYL-5-(TRIFLUOROMETHYL)-1,3,4-THIADIAZOLE

物化性质

• 密度: 1.9±0.1 g/cm3
• 沸点: 707.1±70.0 °C at 760 mmHg
• 熔点: 172 °C(dec.)
• 分子式: C₁₀H₁₂N₄O₅S
• 分子量: 300.291
• 闪点: 381.4±35.7 °C
• 精确质量: 300.052826
• PSA: 130.84000
• LogP: -1.70
• 外观性状: 白色或灰白色粉末
• 蒸汽压: 0.0±2.4 mmHg at 25°C
• 折射率: 1.818
• 储存条件: Store at?0-5°C
• 水溶解性: 水溶性：实际上不溶；可溶于：二甲基甲酰胺；极微溶：乙醇,甲醇
• 分子结构:

  1、 摩尔折射率：49.42

  2、 摩尔体积（cm³/mol）：143.4

  3、 等张比容（90.2K）：416.9

  4、 表面张力（dyne/cm）：71.3

  5、 极化率（10-24cm3）：19.59

• 计算化学:

  1.疏水参数计算参考值（XlogP）:-2

  2.氢键供体数量:1

  3.氢键受体数量:7

  4.可旋转化学键数量:3

  5.互变异构体数量:2

  6.拓扑分子极性表面积131

  7.重原子数量:20

  8.表面电荷:0

  9.复杂度:573

  10.同位素原子数量:0

  11.确定原子立构中心数量:3

  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：白色粉末状结晶

  2.溶解性：几乎不溶于水

生物活性

• 描述: Tazobactam是一种β-内酰胺酶抑制剂, 具有抗菌活性。
• 相关类别:
  信号通路 >> 抗感染 >> 细菌
  研究领域 >> 感染

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : XI0191400 CHEMICAL NAME : 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3-methyl-7-oxo-3-(1H-1,2,3-triazol-1- ylmethyl)-, 4,4-dioxide, (2S-(2-alpha,3-beta,5-alpha))- CAS REGISTRY NUMBER : 89786-04-9 LAST UPDATED : 199612 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C10-H12-N4-O5-S MOLECULAR WEIGHT : 300.32 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Gastrointestinal - hypermotility, diarrhea REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - hypermotility, diarrhea REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - body temperature decrease REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - hematuria REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),145,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14560 mg/kg/26W-I TOXIC EFFECTS : Liver - changes in liver weight Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),155,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 29120 mg/kg/26W-I TOXIC EFFECTS : Biochemical - Metabolism (Intermediary) - other proteins Related to Chronic Data - changes in ovarian weight Related to Chronic Data - changes in uterine weight REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),177,1994 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 33288 mg/kg SEX/DURATION : female 17-21 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth REFERENCE : JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19(Suppl 2),233,1994

安全

• 危害码 (欧洲): Xi: Irritant;
• 风险声明 (欧洲): R36/37/38
• 安全声明 (欧洲): S26-S36/37/39-S45
• 危险品运输编码: UN 1770 8/PG 2
• WGK德国: 3
• 包装等级: II
• 危险类别: 8
• 海关编码: 29036990

合成路线

24138-28-1 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

551-16-6 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

122661-93-2 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

85573-72-4 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

74189-25-6 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

87579-78-0 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

80353-26-0 ~% 89786-04-9

文献：Synthesis, , # 3 art. no. F11904SS, p. 442 - 446

上下游产品

上游产品  6
551-16-6 122661-93-2 85573-72-4 74189-25-6
87579-78-0 80353-26-0
下游产品  2
59703-84-3 89785-84-2

制备

【方法一】
方法1：以舒巴克坦为原料，经酯化保护羧基，再和叠氮钠反应，在3位的一个甲基上引入叠氮基。和乙酸乙烯酯反应，形成三唑化合物，最后氢解脱去保护基，得到三唑巴坦。
上述最后的脱保护基，也可在氢氧化钠作用下脱去。
方法2：以6-APA为原料，经重氮化、溴化，在6位引入溴。过氧乙酸氧化，再酯化后，在锌的作用下脱去溴。然后和三甲基硅基三唑化合物反应，引入三唑化合物，高锰酸钾氧化，最后水解得三唑巴坦钠。
方法3：冰浴冷却和搅拌下，将6-APA、溴化钾和95%乙醇加到硫酸中，在5～7℃下滴加亚硝酸钠溶液，搅拌反应。氯仿萃取3次，萃取液合并，用饱和食盐水洗，浓缩至约1/3体积，得中间体(I)的氯仿溶液。加入水，在0℃下滴加40%过氧乙酸，在0~5℃下搅拌反应。加入二苯腙和碘化钾，在0℃下再加入第二份40%过氧乙酸和10%硫酸，搅拌反应，再在20～25℃下继续反应。分出氯仿层，处理得中间体(Ⅱ)。中间体(Ⅱ)溶于四氢呋喃，加入乙酸铵水溶液，在搅拌和0～5℃下，分批加入锌粉，在20~25℃搅拌反应。加入活性炭和硅藻土，搅拌脱色抽滤，蒸出四氢呋喃。剩余水溶液用乙酸乙酯提取，提取液用饱和氯化钠洗，干燥，浓缩，冷却，抽滤，干燥，得中间体(Ⅲ)，以6-APA计的收率为44.4%。
从中间体(Ⅲ)制中间体(Ⅳ)，参见Synthesis，1986，(4)：292，收率93.9%，含量88%。
从中间体(Ⅳ)制中间体(V)，参见同上，含量88%。
中间体(V)溶于二甲基甲酰胺和乙醇中，在搅拌和5℃下，加入叠氮化钠水溶液，在20～25℃下搅拌反应。倾入冰水，用乙酸乙酯提取。提取液用盐水洗，干燥，浓缩，得(Ⅵa)和(Ⅵb)的混合油状物，直接用于下一步反应。
中间体(Ⅵ)的混合物溶于冰乙酸，加入水，在搅拌和10℃以下，分批加入高锰酸钾，室温搅拌。滴入双氧水以分解过量氧化剂。生成物倒入冰水，抽滤，冷水洗涤，干燥。再溶入乙醚回流后，置冰箱中过夜。(Ⅶb)在冷乙醚中不溶，过滤分离除去。滤液浓缩得(Ⅶa)粗品，用苯一正己烷精制得精品，含量92%。
中间体(Ⅶa)溶于乙酸乙酯，在0.18～0.20MPa的纯乙炔压力和80～85℃下搅拌。冷却，蒸出大部分乙酸乙酯，滤集晶体，用氯仿洗涤，干燥得三唑巴坦二苯甲酯，收率78%。
三唑巴坦二苯甲酯溶于间甲酚，加入碳酸氢钠溶液，在50～55℃下搅拌反应。加入甲基异丁基酮，在0～5℃下再加入碳酸氢钠溶液提取。分出的有机层再用碳酸氢钠溶液提取。碱性水层合并，用甲基异丁基酮洗涤。在冷却和搅拌下，用盐酸调至Ph=1～1.5，得到的白色固体用少量冰水和丙酮洗，干燥得三唑巴坦，收率86%～91%，含量99.1%。三唑巴坦溶于乙酸乙酯，加入异辛酸钠的乙酸乙酯溶液，搅拌。抽滤，乙酸乙酯洗，干燥，得三唑巴坦钠，收率85.7%，含量98.6%，熔点167～169℃(分解)。

海关

海关编码	29036990