联苯双酯 | 73536-69-3

• 物质功能分类: 原料药 - 消化系统用药 - 肝病用药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 中文名称: 联苯双酯
• 中文别名: 4,4'-二甲氧基-5,6,5',6'-双亚甲二氧联苯-2,2'-二甲酸二甲酯；右旋糖酐20；4,4"-二甲氧基-5,6,5",6"-双亚甲二氧联苯-2,2"-二甲酸二甲酯
• 英文名称: DDB
• 英文别名: bifendate；bifendatatum；dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate；methyl 7-methoxy-4-(7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-1,3-benzodioxole-5-carboxylate
• CAS: 73536-69-3
• 化学式: C₂₀H₁₈O₁₀
• 分子量: 418.357
• InChiKey: JMZOMFYRADAWOG-UHFFFAOYSA-N

物化性质

• 熔点：
  179-181 °C
• 沸点：
  606.9±55.0 °C(Predicted)
• 密度：
  1.390±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  10

ADMET

代谢

Bifendate 已知的代谢物包括甲基 4-(2,3-二羟基-4-甲氧基-6-甲氧羰基苯基)-7-甲氧基-1,3-苯并二氧杂环戊烷-5-羧酸酯和单-O-去甲基化 BDD。

Bifendate has known human metabolites that include methyl 4-(2,3-dihydroxy-4-methoxy-6-methoxycarbonylphenyl)-7-methoxy-1,3-benzodioxole-5-carboxylate and Mono-O-demethylated bdd.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2932992000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：0-10°C，需置于惰性气体中，避免与空气接触和加热。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Bifendatatum
Synonyms: 7,7’-Dimethoxy-(4,4’-bi-1,3-benzodioxole)-5,5’-dicarboxylic acid dimethyl ester

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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: Bifendatatum
CAS number: 73536-69-3

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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, refrigerated.
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: C20H18O10
Molecular weight: 418.4

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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.

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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

概述

联苯双酯是我国自主研发的一种治疗肝炎的降酶药物。它具有很高的生物活性，能够显著降低血清谷丙转氨酶（ALT）和谷草转氨酶（AST）水平，增强肝脏解毒功能，并有抗肝细胞坏死的作用。该药物对化疗药物如甲氨蝶呤、5-氟尿嘧啶等引起的中毒性肝炎有明显的治疗效果，且毒性极低，无致畸、致突变效应。药理研究表明联苯双酯还具有一定的抗癌活性。临床主要用于迁延性、慢性肝炎患者以及因药物引起的丙氨酸氨基转移酶持续升高的患者。

作用

联苯双酯能够显著降低丙氨酸氨基转移酶（ALT）水平，对由肝炎或药物引起血清丙氨酸氨基转移酶升高患者具有明显的降酶效果，并且不良反应较少。随疗程延长而逐渐提高降酶效果，尤其对单项丙氨酸氨基转移酶高者效果更佳。对HBsAg阴性者的疗效明显优于阳性者。此外，联苯双酯对肝炎的主要症状有一定改善作用，但对肝、脾肿大无显著影响。

用途

1. 慢性迁延性肝炎：用于丙氨酸氨基转移酶长期增高的患者。
2. 单项丙氨酸氨基转移酶升高：适用于无其他肝功能异常者。
3. 化学药物引起的丙氨酸氨基转移酶升高：可用于治疗由化疗药物等引起的肝损伤。

合成方法

联苯双酯的合成首先通过没食子酸与甲醇在浓硫酸催化下回流得到没食子酸甲酯。将该产物溶于硼砂水溶液中，分别滴加硫酸二甲酯及氢氧化钠溶液进行反应，生成3,4-二羟基-5-甲氧基苯甲酸甲酯。再与二氯甲烷、无水碳酸钾和N,N-二甲基甲酰胺回流反应，得到3,4-亚甲二氧基-5-甲氧基苯甲酸甲酯。最后在氯仿中进行溴化，并通过乌尔曼反应制得联苯双酯。

图1展示了联苯双酯的合成路线。

药动学

联苯双酯口服吸收约30%，肝脏首过效应明显，24小时内约70%由粪便排出。滴丸剂的生物利用度是片剂的1.25～2.37倍。

上述概述、作用、药动学及合成方法信息由Chemicalbook的侍艳编辑整理（2015-12-28）。

禁忌

1. 肝硬化患者。
2. 孕妇及哺乳期妇女。

注意事项

1. 少数病人在用药过程中ALT可回升，加大剂量可能使之降低。停药后部分患者ALT反跳，但继续服药仍有效。
2. 个别患者于服药过程中可出现黄疸及病情恶化，应立即停药。
3. 慢性肝炎患者及老年患者慎用。

药物相互作用

肌苷可以减少联苯双酯的降酶反跳现象。

用途

抗肝炎药物，用于慢性迁延性肝炎、慢性活动性肝炎等疾病的治疗。