87-33-2

• 常用中文名：硝酸异山梨酯
• 常用英文名：isosorbide dinitrate
• CAS号：87-33-2
• 分子式：C₆H₈N₂O₈
• 分子量：236.136
• 相关类别： 原料药 循环系统用药 防治心绞痛药
• 发布时间：2018-04-19 08:00:00
• 更新时间：2024-01-02 18:21:39
• Isosorbide dinitrate (ISDN) 是一种 NO 供体,能防止心肌梗死 (MI) 引起的左室重构和心功能退化。

名称

• 中文名: 硝酸异山梨酯
• 英文名: isosorbide dinitrate
• 中文别名: 异山梨醇硝酸酯; 1,4:3,6-二脱水-D-山梨醇二硝酸酯
• 英文别名: Isorbid; Canranil; vasotrate; isosorbide dinitrate; 1,4:3,6-Dianhydro-2,5-di-O-nitro-D-glucitol; D-Glucitol, 1,4:3,6-dianhydro-, dinitrate; [(3S,3aS,6R,6aS)-3-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate; (3R,3aS,6S,6aS)-Hexahydrofuro[3,2-b]furan-3,6-diyldinitrat; Nitrol (VAN); NITROL; MFCD00868238; dinitrate de (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furane-3,6-diyle; (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate; EINECS 201-740-9

物化性质

• 密度: 1.7±0.1 g/cm3
• 沸点: 365.9±42.0 °C at 760 mmHg
• 熔点: 700C
• 分子式: C₆H₈N₂O₈
• 分子量: 236.136
• 闪点: 186.6±29.9 °C
• 精确质量: 236.028061
• PSA: 128.56000
• LogP: 0.90
• 外观性状: 白色结晶粉末
• 蒸汽压: 0.0±0.8 mmHg at 25°C
• 折射率: 1.538
• 储存条件: 库房低温通风干燥,防火,与氧化剂分开存放
• 分子结构:

  1、 摩尔折射率：44.69

  2、 摩尔体积（cm³/mol）：142.9

  3、 等张比容（90.2K）：402.1

  4、 表面张力（dyne/cm）：62.6

  5、 极化率（10^-24cm³）：17.71

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:0

  3.氢键受体数量:8

  4.可旋转化学键数量:2

  5.互变异构体数量:无

  6.拓扑分子极性表面积129

  7.重原子数量:16

  8.表面电荷:0

  9.复杂度:268

  10.同位素原子数量:0

  11.确定原子立构中心数量:4

  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：白色结晶性粉末。无嗅

  2. 密度（g/mL,25/4℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：70

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率：未确定

  8. 闪点（ºC）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：易溶于氯仿、丙酮，略溶于乙醇，微溶于水

生物活性

• 描述: Isosorbide dinitrate (ISDN) 是一种 NO 供体,能防止心肌梗死 (MI) 引起的左室重构和心功能退化。
• 相关类别:
  研究领域 >> 心血管疾病
  信号通路 >> 免疫及炎症 >> 一氧化氮合酶
• 体内研究: 硝酸异山梨酯(3 mg/kg；气管内；13天)改善心肌梗死后心力衰竭大鼠模型的肺动脉压和心室重构[1]。硝酸异山梨酯后处理对大鼠心肌缺血再灌注损伤具有保护作用[2]。动物模型：5-6周龄雄性幼年Sprague-Dawley大鼠(200-250g)[1]剂量：3mg/kg给药：气管内给药；冠脉结扎后13天结果：心肌缩小,心肌梗死后左、右心室重构减轻。
• 参考文献:

  [1]. Wang X , et al. Intratracheal administration of isosorbide dinitrate improves pulmonary artery pressure and ventricular remodeling in a rat model of heart failure following myocardial infarction. Exp Ther Med. 2017 Aug;14(2):1399-1408.

  [2]. Zhao X, et al. Cardioprotective Effect of Isosorbide Dinitrate Postconditioning Against Rat Myocardial Ischemia-Reperfusion Injury In Vivo. Med Sci Monit. 2019 Mar 2;25:1629-1636.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : LZ4385000 CAS REGISTRY NUMBER : 87-33-2 LAST UPDATED : 199703 DATA ITEMS CITED : 19 MOLECULAR FORMULA : C6-H8-N2-O8 MOLECULAR WEIGHT : 236.16 WISWESSER LINE NOTATION : T55 BO FOTJ DONW HONW HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : Standard Draize test ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rabbit TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 100 ug/kg TOXIC EFFECTS : Behavioral - coma Cardiac - pulse rate Cardiac - other changes TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 747 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 670 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1237 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - excitement TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >40 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1050 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 720 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1050 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >40 mg/kg TOXIC EFFECTS : Behavioral - ataxia Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1080 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >40 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 1109 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 260 mg/kg SEX/DURATION : female 6-22 day(s) after conception lactating female 20 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - sex ratio MUTATION DATA TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Rodent - mouse Mammary gland DOSE/DURATION : 1 mmol/L/48H (Continuous) 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: 5,141,1980 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3175 No. of Facilities: 171 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 2416 (estimated) No. of Female Employees: 1332 (estimated)

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302
• 警示性声明: P301 + P312 + P330
• 危害码 (欧洲): Xn:Harmful;
• 风险声明 (欧洲): R5;R22
• 安全声明 (欧洲): S36
• 危险品运输编码: UN 2907
• 包装等级: II
• 危险类别: 1.1A
• 海关编码: 3004909090

合成路线

652-67-5 ~91% 87-33-2

文献：Bhar, Debjani; Chandrasekaran, Srinivasan Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1997 , vol. 36, # 9 p. 793 - 795

上下游产品

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制备

1.山梨醇溶液经脱水环合，与硝酸酯化而得。

2.制法：

于装有搅拌器、温度计的反应瓶中，加入发烟硝酸50g，浓硫酸7.5g，搅拌下冷却至10℃，慢慢滴加由脱水山梨醇（2）10g（固体）与1mL水微热溶解得到的液体，保持反应液温度在10～15℃，加完后保温反应2h。搅拌下将反应物倒入7倍量的冰水中，充分搅拌析晶。抽滤，水洗至中性，干燥，得粗品。将粗品加入1.5倍量的95%的乙醇中，加热溶解，活性炭脱色回流30min。趁热抽滤，冷至10℃以下，抽滤析出的结晶，乙醇洗涤，低温干燥，得硝酸异山梨醇酯（1），收率70%。

海关

海关编码	2932999099
中文概述	2932999099. 其他仅含氧杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途
Summary	2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%