82009-34-5

• 常用中文名：西司他丁
• 常用英文名：Cilastatin
• CAS号：82009-34-5
• 分子式：C₁₆H₂₆N₂O₅S
• 分子量：358.45300
• 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：2018-05-22 08:00:00
• 更新时间：2024-01-02 20:19:44
• Cilastatin 是一个脱氢肽酶抑制剂。

名称

• 中文名: 西司他丁
• 英文名: cilastatin
• 中文别名: [R-[R^^,S^^(Z)]]-7-[(2-氨基-2-羧基乙基)硫]-2-[[(2,2-二甲基环丙基)羰基]氨基]-2-庚烯酸; (Z)-7-[(2S)-2-氨基-3-羟基-3-氧代丙基]硫-2-[[(1S)-2,2-二甲基环丙甲酰]氨基]庚-2-烯酸; 西司他丁酸
• 英文别名: EINECS 279-875-8; Cilastatin acid; Cilastatine [French]; Cilastatinum; Cilastatine; Cilastatin; Cilastatin Monosodium Salt; Cilastatina [Spanish]; (Z)-7-[(2R)-2-amino-2-carboxyethyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoic acid; MFCD01723686; Cilastatinum [Latin]; [R-[R*,S*-(Z)]]-7-[(2-amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]-2-heptenoic acid; Cilastatina; (Z)-7-[(2R)-(2-amino-2-carboxyethyl)thio]-2-((1S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid

物化性质

• 密度: 1.275 g/cm3
• 沸点: 655.5ºC at 760 mmHg
• 熔点: 156-158ºC
• 分子式: C₁₆H₂₆N₂O₅S
• 分子量: 358.45300
• 精确质量: 358.15600
• PSA: 155.02000
• LogP: 2.52380
• 外观性状: 西司他丁钠(Cilastatin SodiuIn)：C16H25N2NaO5S。[81129-83-1]。类白色至黄白色无定形固体，有吸湿性。极易溶于水或甲醇。pKal2.0，pKa24.4，pKa39.2。
• 折射率: 1.569
• 储存条件: -20°C Freezer
• 稳定性:

  西司他丁钠(Cilastatin SodiuIn)：C16H25N2NaO5S。[81129-83-1]。类白色至黄白色无定形固体，有吸湿性。极易溶于水或甲醇。pKal2.0，pKa24.4，pKa39.2。

• 分子结构:

  1、 摩尔折射率：92.17

  2、 摩尔体积（cm³/mol）：280.9

  3、 等张比容（90.2K）：777.4

  4、 表面张力（dyne/cm）：58.6

  5、 极化率（10-24cm3）：36.54

• 计算化学:

  1.疏水参数计算参考值（XlogP）:-1

  2.氢键供体数量:4

  3.氢键受体数量:7

  4.可旋转化学键数量:11

  5.互变异构体数量:3

  6.拓扑分子极性表面积155

  7.重原子数量:24

  8.表面电荷:0

  9.复杂度:519

  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:1

  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: Cilastatin 是一个脱氢肽酶抑制剂。
• 相关类别:
  信号通路 >> 其他 >> 其他
  研究领域 >> 感染
• 靶点:

  Dehydropeptidase[1]

• 参考文献:

  [1]. The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterialmetallo-beta-lactamase enzyme CphA. Antimicrob Agents Chemother. 1995 Jul;39(7):1629-31.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Cilastatin Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Cilastatin CAS number:82009-34-5 Section4. First aid measures Skin contact:Immediately wash skin with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. If irritation persists, seek medical attention. Eye contact:Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical attention. Inhalation:Remove to fresh air. In severe cases or if symptoms persist, seek medical attention. Ingestion:Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention. Section5. Fire fighting measures In the event of a fire involving this material, alone or in combination with other materials, use dry powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus should be worn. Section6. Accidental release measures Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national standards. Respiratory precaution:Wear approved mask/respirator Hand precaution:Wear suitable gloves/gauntlets Skin protection:Wear suitable protective clothing Eye protection:Wear suitable eye protection Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container for disposal. See section 12. Environmental precautions: Do not allow material to enter drains or water courses. Section7. Handling and storage Handling:This product should be handled only by, or under the close supervision of, those properly qualified in the handling and use of potentially hazardous chemicals, who should take into account the fire, health and chemical hazard data given on this sheet. Store in closed vessels. Storage: Section8. Exposure Controls / Personal protection Engineering Controls: Use only in a chemical fume hood. Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles. General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse. Section9. Physical and chemical properties Appearance:Not specified Boiling point:No data No data Melting point: Flash point:No data Density:No data Molecular formula:C16H26N2O5S Molecular weight:358.5 Section10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, sulfur oxides. Section11. Toxicological information No data. Section12. Ecological information No data. Section13. Disposal consideration Arrange disposal as special waste, by licensed disposal company, in consultation with local waste disposal authority, in accordance with national and regional regulations. Section14. Transportation information Non-harzardous for air and ground transportation. Section15. Regulatory information No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302, or have known CAS numbers that exceed the threshold reporting levels established by SARA Title III, Section 313. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : MJ9650100 CHEMICAL NAME : 2-Heptenoic acid, 7-((2-amino-2-carboxyethyl)thio)-2-(((2,2-dimethylcyc lopropyl)carbonyl) amino)-, (R-(R*,S*-(Z)))- CAS REGISTRY NUMBER : 82009-34-5 LAST UPDATED : 198706 DATA ITEMS CITED : 2 MOLECULAR FORMULA : C16-H26-N2-O5-S MOLECULAR WEIGHT : 358.50 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 8 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PHINDQ Pharmacy International. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1980- Volume(issue)/page/year: 5,133,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 8 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PHINDQ Pharmacy International. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1980- Volume(issue)/page/year: 5,133,1984

安全

• 危害码 (欧洲): Xi
• 风险声明 (欧洲): R36/37/38:Irritating to eyes, respiratory system and skin .
• 安全声明 (欧洲): S26-S36
• WGK德国: 3

合成路线

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制备

2,2-二乙氧基乙酸乙酯和1,3-丙二硫醇反应，得1,3-二噻烷-2-羧酸乙酯，收率69.4%。然后在氢化钠作用下，和1,5-二溴戊烷反应，得2-(5-溴戊基)-1,3-二噻烷-2-羧酸乙酯。接着和溴化琥珀酰亚胺(NBS)反应，得7-溴-2-氧代庚酸乙酯。酸性水解即得7-溴-2-氧代庚酸，收率69%(以1,3-二噻烷-2-羧酸乙酯计)。
2,2-二甲基-1,3-丙二醇和对甲苯磺酰氯进行酯化反应，生成二对甲苯磺酸酯，收率94.3%。再在氰化钾作用下环合，生成2，2-二甲基环丙烷甲腈，收率64.9%。氢氧化钾水溶液碱性水解，得外消旋的2，2-二甲基环丙烷羧酸，收率几乎定量。外消旋物用左旋奎宁进行拆分，得纯的(S)构型，收率14.1%。然后和N-三氟乙酰氧基丁二酰亚胺反应，生成(+)-N-[(2,2一二甲基环丙烷)甲酰氧基]丁二酰亚胺，收率90.5%。该亚胺化合物为活性酯化合物，其反应活性大，氨解即得(+)-(S)-2,2-二甲基环丙烷甲酰胺，收率83%。
7-溴-2-氧代庚酸和(+)-(S)-2,2-二甲基环丙烷甲酰胺在甲苯中回流，生成的产物(收率25%)再和L-胱氨酸反应，即得西司他丁，收率63%， [α]_D²³+18.0°(C=0.54，甲醇)。