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：2024-01-01 20:11:31
• 【用途一】
  青霉烷砜类β-内酰胺酶抑制剂，对I～Ⅵ型3-内酰胺酶均有效，特别是对I型酶更为有效。其毒性低，稳定性好，抑酶活性强。临床用于治疗多种细菌包括需氧菌和厌氧菌引起的感染，包括下呼吸道感染、皮肤和腹部感染等。
  【用途二】
  β-内酰胺酶抑制剂，第三代抗菌强增效剂，与哌拉西林或头孢哌酮合用可增强二者的药效及延长作用时间 。他唑巴坦钠与哌拉西林钠联合使用时，产生明显的协同作用，广泛用于治疗严重全身性和局部感染、腹腔感染、下呼吸道感染、软组织感染、败血症等，比已使用的其它抗菌复合剂具有更广泛的抗菌谱及适应症，克服耐药性显示了巨大优势。

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。

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:(1) 6a-溴青霉烷-3a-羧酸(012-1)的制备

在反应瓶中加2.5mol/L硫酸500ml,,搅拌下冷却到约10ºC,加入6-氨基青霉烷酸(6-APA)43.2g(0.2mol)和溴化钾120.2g,然后再加入95%乙醇400ml,将混合物冷却到6-8ºC,滴加亚硝酸钠21.2g溶于水100ml的溶液,在1h内滴加完#保持混合物温度在6-8ºC搅拌3.5h反应毕,用氯仿(2*250ml,4*100ml,3*50ml)提取,合并氯仿层,用50%冷盐水(2*250ml)洗,无水硫酸钠干燥,过滤,滤液浓缩,得到012-1黏稠泡沫状物49.96g,收率89%.
(2)6a-溴青霉烷-3a-羧酸二苯甲酯-1B-氧化物(012-2)的制备

在反应瓶中加入012-1 22.4g(0.08mol)、二苯腙17.5g(0.09mol）和氯仿200ml,搅拌溶解,再加入
80%甲酸3.90g(0.072mol)和30%双氧水10.6g(0.094mol),冷却到5ºC加入90%多聚磷酸(H6P4O13)3.75g(0.01mol),搅拌4h,TLC监控012-1基本消失.反应液用2.8%碳酸氢钠和1.7%亚硫酸氢钠溶液(3*40ml)洗,水洗(2*40ml)至中性,无水硫酸钠干燥,过滤,滤液减压下蒸除溶剂,加入环己烷/乙酸乙酯(8:1)150ml,白色固体过滤抽干,干燥,得012-2 30.33g收率80%,mp148~150ºC.

(3)青霉烷-3a-羧酸二苯甲酯-1B-氧化物(012-3)的制备
在反应瓶中加入(012-2)33.58g(0.0726mol)和
THF180ml,搅拌溶解,再加入乙酸铵溶液(22.78g溶于水182ml),分批加入锌粉15(0.237mol),室温搅拌反应1h后,TLC监控012-2消失,减压蒸除THF,加入乙酸乙酯200ml提取,提取液用饱和氯化钠溶液100ml洗至中性,无水硫酸钠干燥,过滤,滤液减压蒸除溶剂,加入环己烷-乙酸乙酯(8:1)150ml,析出白色固体,过滤,干燥,得012-3 22.3g,收率80.1%,mp149~151ºC.

(4)2a-甲基-2B-(1,2,3-三唑-1-基)甲基青霉烷-3a-羧酸二苯甲酯(012-4)的制备

在微型压热釜中加入012-3 19.2g(0.05mol)、2-三甲基硅-1，2，3-三唑7.2（0.051mol）和甲苯180ml,搅拌(或振摇)下通入氮气排去釜内空气,充氮密闭,加热至116~120 ºC反应4h.冷却,取出反应液蒸除甲苯(减压下),剩余物用乙酸乙酯250ml提取，水（8ml）洗,氯化钠溶液(80ml)洗,无水硫酸钠干燥,过滤,滤液减压蒸除溶剂,剩余物用乙醇重结晶,得012-4白色固体12.1g,收率55.7%,mp140~142 ºC

2-三甲基硅-1,2,3-三唑按文献[8]法制得,该化合物为无色油状物,经溶剂结晶mp147~148 ºC

(5).2a-甲基-2B-(1,2,3-三唑-1-基)甲基青霉烷-3a-羧酸二苯甲酯1,1-二氧化物(012-5)的制备

在反应瓶中加入012-4 10.86g(0.025mol)和丙酮10ml,搅拌,加水23ml和冰醋酸32ml,冷却至0~5 ºC ,再加入高锰酸钾7.9g(0.05mol),室温搅拌反应3h.滴加30%双氧水至反应液无色,过滤析出固体,甲醇重结晶,得白色固体10.5g(012-5),收率90%.mp205~207 ºC

(6).他唑巴坦(012)的合成

在反应瓶中加入012-5 10.5g(0.0225mol)与间甲基苯酚85ml,拌均匀,加热到80 ºC 保持反应3h反应毕,冷却至室温,用甲基异丁基酮80ml溶解,用20%碳酸氢钠水溶液洗,分出水层,冷却至0~5 ºC ,用6mol/L盐酸调PH至1.8，析出固体过滤收集，水洗（冰水），丙酮洗抽干，干燥，得白色粉末结晶012 5.6g,mp136~138 ºC .收率82.3%.

将他唑巴坦(012)溶于乙酸乙酯,加入异辛酸钠的乙酸乙酯溶液,搅拌#过滤,乙酸乙酯洗,干燥,得他唑巴坦钠,收率85.7%,mp167~169 ºC (分解).含量98.6%.

海关

海关编码	29036990