147444-03-9

• 常用中文名：啶南平A
• 常用英文名：Pyripyropene A
• CAS号：147444-03-9
• 分子式：C₃₁H₃₇NO₁₀
• 分子量：583.626
• 相关类别： 研究领域 心血管疾病
• 发布时间：2018-04-03 08:00:00
• 更新时间：2024-01-09 21:54:44
• Pyripyropene A 是一种高效、选择性的 SOAT2/ACAT2 抑制剂,其 IC50 值为 0.07 µM。Pyripyropene A 在体内能减轻高胆固醇血症和动脉粥样硬化。

名称

• 中文名: 啶南平A
• 英文名: pyripyropene A
• 英文别名: Homopurine; 1,3,5,7-Tetraazanaphthalene; (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-(Acetoxymethyl)-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(pyridin-3-yl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate; (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-(Acetoxymethyl)-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate; 2H,11H-Naphtho[2,1-b]pyrano[3,4-e]pyran-11-one, 3,6-bis(acetyloxy)-4-[(acetyloxy)methyl]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-12-hydroxy-4,6a,12b-trimethyl-9-(3-pyridinyl)-, (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-; pyripropen A; Pyrimidopyrimidin

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 690.8±55.0 °C at 760 mmHg
• 熔点: 153-154°C (lit.)
• 分子式: C₃₁H₃₇NO₁₀
• 分子量: 583.626
• 闪点: 371.6±31.5 °C
• 精确质量: 583.241760
• PSA: 151.46000
• LogP: 2.68
• 外观性状: 固体
• 蒸汽压: 0.0±2.3 mmHg at 25°C
• 折射率: 1.587
• 储存条件: 室温

生物活性

• 描述: Pyripyropene A 是一种高效、选择性的 SOAT2/ACAT2 抑制剂,其 IC50 值为 0.07 µM。Pyripyropene A 在体内能减轻高胆固醇血症和动脉粥样硬化。
• 相关类别:
  研究领域 >> 心血管疾病
  研究领域 >> 感染
  研究领域 >> 炎症/免疫
• 靶点:

  IC50: 0.07 µM (ACAT2)[1]

• 体外研究: 吡咯烷酮A(0-100μM；72小时)对人脐静脉内皮细胞具有抗增殖活性,IC50值为1.8μM[1]。吡咯烷酮A(10μM；24小时)以剂量依赖的方式抑制VEGF(20 ng/ml)诱导的huvec迁移和管状形成[1]。吡咯烷酮A对KB3-1、K562和神经2a细胞无生长抑制作用[1]。细胞增殖试验[1]细胞系：HUVECs浓度：0-100μM培养时间：72小时结果：对HUVECs具有抗增殖活性,IC50值为1.8μM。
• 体内研究: 吡咯烷酮A(10-50 mg/kg/天；p.o；12周)降低载脂蛋白E基因敲除小鼠血浆胆固醇、极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)和肝胆固醇含量。吡咯烷酮A治疗的小鼠显示主动脉和心脏的致动脉粥样硬化病变区域减少[3]。吡咯烷酮A抑制肝脏e酰基辅酶A:胆固醇酰基转移酶2(ACAT2)在体内的活性[3]。吡咯烷酮A的半衰期(t1/2)为0.693/λ,其中λ表示浓度-时间曲线对数线性部分的终端斜率[4]。动物模型：雄性C57BL/6小鼠[2]剂量：0 mg/kg、1 mg/kg、10 mg/kg、50 mg/kg、100 mg/kg；口服；每日；12周结果：主动脉和心脏动脉粥样硬化病变面积减少。动物模型：9周龄雄性ICR小鼠(药代动力学分析)[4]剂量：5mg/kg,10mg/kg给药：口服给药结果：t1/2=0.693/λ
• 参考文献:

  [1]. Hayashi A, et al. Pyripyropenes, fungal sesquiterpenes conjugated with alpha-pyrone and pyridine moieties, exhibits anti-angiogenic activity against human umbilical vein endothelial cells. Biol Pharm Bull. 2009 Jul;32(7):1261-5.

  [2]. Ohtawa M, et al. Design and Synthesis of A-Ring Simplified Pyripyropene A Analogues as Potent and Selective Synthetic SOAT2 Inhibitors. ChemMedChem. 2018 Mar 6;13(5):411-421.

  [3]. Ohshiro T, et al. Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1108-15.

  [4]. Lee KR , et al. Determination of Penicillium griseofulvum-oriented pyripyropene A, a selective inhibitor of acyl-coenzyme A:cholesterol acyltransferase 2, in mouse plasma using liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies. Biomed Chromatogr. 2019 Feb;33(2):e4388.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : QL6289000 CHEMICAL NAME : 2H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-11-one, 1,3,4,4a,5,6a,12,12a,12b-decahydro-4- ((acetyloxy)methyl)-3,6-bis(acetyloxy)-12-hydroxy-9-( 3-pyridinyl)-4,6a,12b -trimethyl- CAS REGISTRY NUMBER : 147444-03-9 LAST UPDATED : 199509 DATA ITEMS CITED : 1 MOLECULAR FORMULA : C31-H37-N-O10 MOLECULAR WEIGHT : 583.69 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 47,148,1994