111025-46-8

• 常用中文名：匹格列酮
• 常用英文名：Pioglitazone
• CAS号：111025-46-8
• 分子式：C₁₉H₂₀N₂O₃S
• 分子量：356.44
• 相关类别： 生物化工 抑制剂 代谢(Metabolism) PPAR 激动剂
• 发布时间：2018-05-12 08:00:00
• 更新时间：2024-01-03 08:44:37
• 用于治疗(Ⅱ)型糖尿病

名称

• 中文名: 匹格列酮
• 英文名: pioglitazone
• 中文别名: 5-[[4-[2-(5-乙基吡啶-2-基)乙氧基]苯基]甲基]-1,3-噻唑烷-2,4-二酮
• 英文别名: 2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-; 2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]- (9CI); 5-[[4-[2-[(5-ethyl-2-pyridyl)]ethoxy]phenyl]methyl]thiazolidine- 2,4-dione; 5-{4-[2-(5-Ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione; Actos; Pioglitazone; 5-{4-[2-(5-Ethyl-2-pyridinyl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione; Pioglitazone [Ban:Inn]; 2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-, (±)-; 5-((4-(2-(5-Ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-2,4-thiazolidinedione; 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-Thiazolidinedione

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 575.4±45.0 °C at 760 mmHg
• 熔点: 183-184ºC
• 分子式: C₁₉H₂₀N₂O₃S
• 分子量: 356.44
• 闪点: 301.8±28.7 °C
• PSA: 93.59000
• LogP: 2.94
• 外观性状: 白色粉末
• 蒸汽压: 0.0±1.6 mmHg at 25°C
• 折射率: 1.611
• 储存条件:

  密闭于阴凉干燥环境中

• 稳定性:

  遵照规定使用和储存则不会分解。

• 分子结构:

  1、 摩尔折射率：98.21

  2、 摩尔体积（cm³/mol）：282.7

  3、 等张比容（90.2K）：769.7

  4、 表面张力（dyne/cm）：54.9

  5、 极化率（10^-24cm³）：38.93

• 计算化学:

  1.疏水参数计算参考值（XlogP）:3.8

  2.氢键供体数量:1

  3.氢键受体数量:5

  4.可旋转化学键数量:7

  5.互变异构体数量:10

  6.拓扑分子极性表面积93.6

  7.重原子数量:25

  8.表面电荷:0

  9.复杂度:466

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:1

  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：无色针状晶体

  2. 密度（g/mL,25/4℃）：无可用

  3. 相对蒸汽密度（g/mL,空气=1）：无可用

  4. 熔点（ºC）：183-184

  5. 沸点（ºC,常压）：无可用

  6. 沸点（ºC,5.2kPa）：无可用

  7. 折射率：无可用

  8. 闪点（ºC）：无可用

  9. 比旋光度（º）：无可用

  10. 自燃点或引燃温度（ºC）：无可用

  11. 蒸气压（kPa,25ºC）：无可用

  12. 饱和蒸气压（kPa,60ºC）：无可用

  13. 燃烧热（KJ/mol）：无可用

  14. 临界温度（ºC）：无可用

  15. 临界压力（KPa）：无可用

  16. 油水（辛醇/水）分配系数的对数值：无可用

  17. 爆炸上限（%,V/V）：无可用

  18. 爆炸下限（%,V/V）：无可用

  19. 溶解性：无可用

生物活性

• 描述: Pioglitazone 是一种有效的选择性 PPARγ 激动剂,高亲和力结合到 PPARγ 配体结合域。作用于人和鼠 PPARγ,EC50 分别为 0.93 和 0.99 μM。
• 相关类别:
  天然产物 >> 生物碱
  研究领域 >> 代谢疾病
• 靶点:

  PPARδ:0.01 μM (EC50, Human PPARδ)

  PPARα:0.93 μM (EC50, Human PPARα)

  PPARγ:43 μM (EC50, Human PPARγ)

• 体外研究: 通过向AGEs培养基中添加吡格列酮,完全消除了AGEs诱导的β细胞坏死。此外,吡格列酮完全阻止任何AGEs诱导的胱天蛋白酶-3活化增加,从而将胱天蛋白酶-3活性恢复到与对照细胞相同的水平。正如预期的那样,AG能够抵抗AGEs诱导的活力受损[2]。
• 体内研究: 在10mg/kg吡格列酮后,ob/ob和adipo -/- ob/ob小鼠中的无血清脂肪酸和甘油三酯水平以及脂肪细胞大小没有变化,但在30mg/kg吡格列酮后显着降低至相似程度。此外,ob/ob和adipo -/- ob/ob小鼠的脂肪组织中TNFα和抵抗素的表达在10mg/kg吡格列酮后没有变化,但在30mg/kg吡格列酮后降低。因此,吡格列酮诱导的胰岛素抵抗和糖尿病的改善可能在肝脏和脂联素中依赖于脂联素在骨骼肌中独立发生[3]。吡格列酮(10mg/kg每天)治疗显着减轻体重(BW)和心脏肥大的损失。吡格列酮治疗显着降低血清葡萄糖水平升高并显着改善相关的血脂异常。此外,与对照组相比,D大鼠血清肌酐水平略有但显着增加(P <0.05)。然而,在糖尿病肾病(DN)组中观察到明显的肾功能障碍(P <0.05)。此外,相对于N和D大鼠,DN大鼠表现出最高的CK-MB血清活性(P <0.05)。吡格列酮能够降低肌酐和肌酸激酶-MB(CK-MB)的血清水平升高[4]。
• 细胞实验: 为了评估细胞增殖，将HIT-T15细胞接种在96孔板（3×10 4细胞/孔）上并如所述培养5天。使用Cell Titer 96 Aqueous One Solution Cell Proliferation Assay测定活细胞。为了评估细胞凋亡和细胞坏死，将HIT-T15细胞在标准条件（CTR）或有或没有吡格列酮的AGEs（AGEs）存在下在6孔培养皿（7×105细胞/孔）上接种5天（ 0.5或1μM）或AG（1mM）。然后使用细胞毒素96非放射性细胞毒性测定法处理它们以测量胱天蛋白酶-3的活性和乳酸脱氢酶（LDH）的活性（稳定的细胞溶质酶，其是细胞膜损伤的标记物和由于坏死导致的细胞死亡）。 2]。
• 动物实验: 将小鼠[3] 10mg / kg盐酸吡格列酮或载体（0.25％羧甲基纤维素）通过口服管饲法每天一次给予ob / ob和adipo - / - ob / ob小鼠连续14天。 30mg / kg吡格列酮或媒介物也通过口服强饲法每天一次给予ob / ob和adipo - / - ob / ob小鼠连续14天。大鼠[4]使用雄性Wistar白化大鼠（体重250±20 g）。血清葡萄糖水平≥250mg/ dL，血清肌酐水平≥1.5mg/ dL的大鼠分为2组（每组n = 10） ）：糖尿病肾病（DN）组，其中大鼠接受等量的媒介物（0.5％羧甲基纤维素）和吡格列酮治疗（DN + Pio）组，其中用吡格列酮治疗大鼠。吡格列酮（10mg / kg BW）通过胃管饲法口服给药，每日一次，持续4周。
• 参考文献:

  [1]. Kuwabara K, et al. A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose leve

  [2]. Puddu A, et al. Pioglitazone attenuates the detrimental effects of advanced glycation end-products in the pancreatic beta cell line HIT-T15. Regul Pept. 2012 Aug 20;177(1-3):79-84.

  [3]. Kubota N, et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem. 2006 Mar 31;281(13):8748-55.

  [4]. Elrashidy RA, et al. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. J Cardiovasc Pharmacol Ther. 2012 Sep;17(3):324-33.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Pioglitazone Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Pioglitazone CAS number:111025-46-8 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, refrigerated. 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:C19H20N2O3S Molecular weight:356.4 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

生态学数据: 该物质对环境可能有危害，对水体应给予特别注意。

安全

• 危害码 (欧洲): F,C
• 风险声明 (欧洲): R20/21/22
• 安全声明 (欧洲): S36/37

制备

2-(5-乙基-2-吡啶基)乙醇(Ⅰ)和对氟硝基苯缩合，得到化合物(Ⅱ)。接着还原为胺(Ⅲ)，然后在含氢溴酸的丙酮-甲醇中重氮化，再加入丙烯酸甲酯偶合得到化合物(Ⅳ)。继而和硫脲缩合环合，再水解得到吡格列酮。