7-[(2-Amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl)-oxomethyl]amino]-2-heptenoic acid | 82009-34-5

• 物质功能分类: 原料药 - 抗生素类药物 - β-内酰胺酶抑制剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 7-[(2-Amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl)-oxomethyl]amino]-2-heptenoic acid
• 英文别名: 7-(2-amino-2-carboxyethyl)sulfanyl-2-[(2,2-dimethylcyclopropanecarbonyl)amino]hept-2-enoic acid
• CAS: 82009-34-5
• 化学式: C₁₆H₂₆N₂O₅S
• 分子量: 358.5
• InChiKey: DHSUYTOATWAVLW-UHFFFAOYSA-N

物化性质

• 熔点：
  156-158°C
• 沸点：
  655.5±55.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）
• 稳定性/保质期：
  西司他丁钠（Cilastatin Sodium）：化学式为C16H25N2NaO5S，CAS号为81129-83-1。这是一种类白色至黄白色的无定形固体，具有吸湿性，极易溶于水或甲醇。其pKa值分别为2.0、4.4和9.2。

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• 危险品标志：
  Xi
• WGK Germany：
  3
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C冷冻库

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Cilastatin
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Cilastatin
CAS number: 82009-34-5

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Section 4. 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.

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Section 5. 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.

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Section 6. 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.

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Section 7. 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:

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Section 8. 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.

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Section 9. 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

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Section 10. 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.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. 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.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. 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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性 Cilastatin (MK0791) 是一种可逆的竞争性肾脏脱氢肽酶 I (renal dehydropeptidase I) 抑制剂，IC50 为 0.1 μM。它能抑制细菌金属叶内酰胺酶 CphA 的活性，其 IC50 值为 178 μM。Cilastatin 可用作抗菌辅助剂。

靶点

• dehydropeptidase-I
• leukotriene D4 dipeptidase

体外研究 Cilastatin (200 μg/mL; 24 hours) 处理能保护范科米星诱导的近端肾小管细胞凋亡，增加细胞存活率而不影响范科米星的抗菌效果。具体来说：

• 细胞系：肾小管上皮细胞 (RPTECs)
• 浓度：200 μg/mL
• 孵育时间：24 小时
• 结果：显著缓解了范科米星诱导的核凋亡。

体内研究 在实验性全身感染模型中（雌性 CD-1 鼠，体重 20 g），Cilastatin 联合亚胺培南能够保护小鼠免受金黄色葡萄球菌 (S. aureus)、大肠杆菌 (E. coli) 和铜绿假单胞菌 (P. aeruginosa) 的感染。

化学性质 西司他丁钠 (Cilastatin Sodium)：C16H25N2NaO5S。[81129-83-1]。为类白色至黄白色无定形固体，极易溶于水或甲醇。pKa 值分别为 2.0、4.4 和 9.2。

用途 作为肾肽酶抑制剂，与碳青霉烯类抗生素亚胺培南配伍使用时，通过特异性抑制肾肽酶的作用，避免其对亚胺培南的降解，从而提高后者活性。Cilastatin 氯化钠和亚胺培南 (1:1) 的复方制剂为泰宁 (Tienan；Primaxin)。

生产方法

• 2,2-二乙氧基乙酸乙酯与 1,3-丙二硫醇反应，产率 69.4%。

• 在氢化钠作用下，与 1,5-二溴戊烷反应生成 2-(5-溴戊基)-1,3-二噻烷-2-羧酸乙酯。

• 溴化琥珀酰亚胺 (NBS) 反应得到 7-溴-2-氧代庚酸乙酯，产率 69%（基于 1,3-二噻烷-2-羧酸乙酯）。

• 酸性水解得到 7-溴-2-氧代庚酸，产率 69%。

• 2,2-二甲基-1,3-丙二醇与对甲苯磺酰氯反应生成二对甲苯磺酸酯，产率 94.3%。

• 环合生成 2,2-二甲基环丙烷甲腈，产率 64.9%。

• 氢氧化钾水溶液碱性水解得到外消旋的 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拆分得纯 (S) 构型，产率 14.1%。

• 螺旋化合物与 N-三氟乙酰氧基丁二酰亚胺反应生成 (+)-N-[2,2-二甲基环丙烷]甲酰氧基]丁二酰亚胺，产率 90.5%。

• 氨解得到 (+)-(S)-2,2-二甲基环丙烷甲酰胺，收率 83%。

7-溴-2-氧代庚酸与 (+)-(S)-2,2-二甲基环丙烷甲酰胺在甲苯中回流反应生成产物（产率 25%），再与 L-胱氨酸反应得到西司他丁，收率 63%，[α]D23+18.0°(C=0.54, MeOH)。