盐酸罂粟碱杂质18 | 75608-42-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 盐酸罂粟碱杂质18
• 英文名称: N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(3-hydroxy-4-methoxyphenyl)acetamide
• 英文别名: N-(3,4-dimethoxyphenethyl)-2-(3-hydroxy-4-methoxyphenyl)acetamide
• CAS: 75608-42-3
• 化学式: C₁₉H₂₃NO₅
• 分子量: 345.395
• InChiKey: GWASPJJCNIVRTH-UHFFFAOYSA-N

物化性质

• 熔点：
  125-127 °C(Solv: ethanol (64-17-5))
• 沸点：
  586.1±50.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  盐酸罂粟碱杂质18 在 lithium aluminium tetrahydride 作用下， 以 甲基叔丁基醚 为溶剂， 以14%的产率得到5-{2-[2-(3,4-dimethoxyphenyl)ethylamino]ethyl}-2-methoxyphenol
  参考文献：
  名称：

  A New Class of Selective and Potent 7-Dehydrocholesterol Reductase Inhibitors

  摘要：

  We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished by a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis. In a whole-cell assay, the most active compound 5f showed a much stronger inhibition of overall cholesterol biosynthesis (IC50 2.3 nM) than BM 15.766 (IC50 500 nM), presently the most selective known inhibitor of 7-DHCR Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli-Opitz syndrome (SLOS), the potent and selective inhibitors reported here will enable more detailed investigation of the pathogenesis of SLOS.

  DOI：

  10.1021/jm3006096
• 作为产物：
  描述：

  (3-苄氧基-4-甲氧基-苯基)乙酸 在 palladium on activated charcoal 盐酸 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 16.5h， 生成 盐酸罂粟碱杂质18
  参考文献：
  名称：

  McDonald, Edward; Wylie, Robert D., Journal of the Chemical Society. Perkin transactions I, 1980, p. 1104 - 1108

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING NASH, NAFLD, AND OBESITY<br/>[FR] COMPOSÉS, COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA NASH, DE LA NAFLD ET DE L'OBÉSITÉ
  申请人：LIU JINGWEN

  公开号：WO2021067490A1

  公开（公告）日：2021-04-08

  The present technology relates to methods of treating NASH, NAFLD and/or obesity using compounds of Formulas I, II, III, IV, V, and/or VI. The methods include administering to a subject suffering from one or more of non-alcoholic steatohepatitis (NASH), non- alcoholic fatty liver disease (NAFLD) and/or obesity a therapeutically effective amount of such a compound

  目前的技术涉及使用I、II、III、IV、V和/或VI式化合物治疗NASH、NAFLD和/或肥胖的方法。这些方法包括向患有非酒精性脂肪肝炎（NASH）、非酒精性脂肪肝病（NAFLD）和/或肥胖的受试者施用这种化合物的治疗有效剂量。
• COMPOUNDS, COMPOSITIONS AND METHODS FOR REDUCING LIPID LEVELS
  申请人：Liu Haiyan

  公开号：US20090048246A1

  公开（公告）日：2009-02-19

  Compositions comprising extracts or isolated or purified compounds from plants of the genus Corydalis provide prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Corydalis compounds and their derivatives of natural and synthetic origins lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression and activate AMP-activated protein kinase. Specific stereoisomers of Corydalis compounds with lipid lowering activity include 14R-(+)-corypalmine, 14R,13S-(+)-corydaline, 14R-(+)-tetrahydropalmatin, (+)-corlumidin, d-(+)-bicuculline, and (+)-egenine.

  从黄堇属植物提取物或分离纯化的化合物构成的组合物可预防和治疗高脂血症、高胆固醇血症、高甘油三酯血症、肝脂肪变性和代谢综合征。黄堇化合物及其天然和合成来源的衍生物可降低总胆固醇、LDL-胆固醇和甘油三酯，增加肝LDL受体表达并激活AMP激活蛋白激酶。具有降脂活性的黄堇化合物的特定立体异构体包括14R-(+)-可丹碱、14R,13S-(+)-可丹啉、14R-(+)-四氢棕榈碱、(+)-可鲁米丁、d-(+)-比库枯碱和(+)-艾根碱。
• [EN] CORYDALINE DERIVATIVES USEFUL FOR REDUCING LIPID LEVELS<br/>[FR] DÉRIVÉS DE CORYDALINE UTILES DANS LA RÉDUCTION DES TAUX LIPIDIQUES
  申请人：CVI PHARMACEUTICALS LTD

  公开号：WO2010075469A1

  公开（公告）日：2010-07-01

  The present technology relates to compounds of Formulas (V) and (VI) and methods of making and using such compounds. Methods of use include prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Compounds disclosed herein also lower total cholesterol, LDL- cholesterol, and triglycerides and increase hepatic LDL receptor expression, inhibit PCSK9 expression, and activate AMP-activated potein kinase.

  目前的技术涉及到公式（V）和（VI）的化合物以及制备和使用这些化合物的方法。使用方法包括预防和治疗高脂血症、高胆固醇血症、高甘油三酯血症、肝脂肪变性和代谢综合征。本文披露的化合物还能降低总胆固醇、LDL-胆固醇和甘油三酯，增加肝LDL受体表达，抑制PCSK9表达，并激活AMP激活的蛋白激酶。
• Flow Conditions‐Controlled Divergent Oxidative Cyclization of Reticuline‐Type Alkaloids to Aporphine and Morphinandienone Natural Products
  作者：Bi Bali Judicaël Tra、Abollé Abollé、Vincent Coeffard、François‐Xavier Felpin

  DOI：10.1002/ejoc.202200301

  日期：2022.6.13

  We describe a divergent continuous-flow approach for the biomimetic oxidative cyclization of reticuline-type alkaloids to aporphine and morphinandienone natural products using hypervalent iodine compounds.

  我们描述了一种使用高价碘化合物将网状生物碱仿生氧化环化为阿吗啡和吗啡二烯酮天然产物的发散连续流动方法。
• Simplified Derivatives of Tetrandrine as Potent and Specific P-gp Inhibitors to Reverse Multidrug Resistance in Cancer Chemotherapy
  作者：Rong Zeng、Xiu-Ming Yang、Hong-Wei Li、Xue Li、Yu Guan、Tao Yu、Peng Yan、Wen Yuan、Sheng-Li Niu、Jing Gu、Ying-Chun Chen、Qin Ouyang

  DOI：10.1021/acs.jmedchem.2c02061

  日期：2023.3.23

  Targeted inhibition of a drug efflux transporter P-glycoprotein (P-gp) is an important strategy to reverse multidrug resistance in cancer chemotherapy. In this study, a rationally structural simplification to natural tetrandrine was performed based on molecular dynamics simulation and fragment growth, leading to an easily prepared, novel, and simplified compound OY-101 with high reversal activity and

  靶向抑制药物外排转运蛋白 P-糖蛋白 (P-gp) 是逆转癌症化疗中多药耐药性的重要策略。本研究基于分子动力学模拟和片段生长对天然粉防己碱进行了合理的结构简化，得到了一种易于制备、新颖且简化的化合物OY-101，具有高逆转活性和低细胞毒性。通过逆转活性测定、流式细胞术、平板克隆形成测定和药物协同分析证实其与长春新碱（VCR）对耐药细胞Eca109/VCR具有优异的协同抗癌作用（IC 50 = 9.9 nM，RF = 690） 。进一步的机制研究证实OY-101是一种特异性、高效的P-gp抑制剂。重要的是，OY-101增加了体内VCR 致敏性，但没有明显的毒性。总体而言，我们的研究结果可能为设计新型特异性 P-gp 抑制剂作为抗肿瘤化疗增敏剂提供替代策略。