7-苄氧基喹啉 | 131802-60-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 7-苄氧基喹啉
• 中文别名: 7-(苄氧基)异喹啉
• 英文名称: 7-Benzyloxyquinoline
• 英文别名: 7-phenylmethoxyquinoline
• CAS: 131802-60-3
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: SIDLHXXVIBTSJZ-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

7-苄氧基喹啉已知的人类代谢物包括7-羟基喹啉。

7-benzyloxyquinoline has known human metabolites that include 7-Hydroxyquinoline.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

反应信息

• 作为反应物：
  描述：

  7-苄氧基喹啉 在 phosphate buffer 、 human liver microsomes 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 反应 0.33h， 生成 7-羟基喹啉
  参考文献：
  名称：

  Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by human hepatic CYP isoforms: evidence for selectivity towards CYP3A4

  摘要：

  1. The metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin (BFBFC) to 7-hydroxy-4-trifluoromethylcourmarin (HFC) was studied in human liver microsomes and in cDNA-expressed human liver CYP isoforms. For purpose of comparsion, some limited studies were also performed with 7-benzyloxyquinoline (7BQ).2. Initial interactive docking studies with a homology model of human CYP3A4 indicated that BFBFC was likely to be a selective substrate for CYP3A4 with a relatively high binding affinity, due to the presence of several key hydrogen bonds with active site amino acid residues.3. Kinetic analysis of NADPH-dependent BFBFC metabolism to HFC in three preparation of pooled human liver microsomes revealed mean (+/- SEM) K-m and V-max = 4.6 +/-0.3 muM and 20.0 +/-3.8 pmol/min/mg protein, respectively.4. The metabolism of BFBFC to HFC was determined in a characterized bank of 24 individual human liver microsomal preparations employing a BFBFC substrate concentration of 10 muM (i.e. around twice K-m). Good correlations (r(2) = 0.736-0.904) were observed between BFBFC metabolism and markers of CYP3A isoforms.5. While 10 mum BFBFC was metabolized to HFC by cDNA-expressed CYP3A4, little or no metabolism was observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1.6. The metabolism of 10 muM BFBFC in human liver microsomes was markedly inhibited by 5-50 muM troleandomycin and 0.2-5 muM ketoconazole, but stimulated by 0.2-10 muM alpha -naphthoflavone. The metabolism of 10 muM BFBFC in human liver microsomes was also markedly inhibited by an antibody to CYP3A4.7. Kinetic analysis of NADPH-dependent 7BQ metabolism to 7-hydroxyquinoline (7HQ) in human liver microsomes revealed K-m and V-max = 70 muM and 3.39 nmol/min/mg protein, respectively.8. While 80 muM 7BQ was metabolized to 7HQ by cDNA-expressed CYP3A4, only low rates of metabolism were observed with cDNA-expressed CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1.9. In summary, by correlation analysis, the use of cDNA-expressed CYP isoforms, chemical inhibition and inhibitory antibodies, BFBFC metabolism in human liver microsomes appears to be primarily catalysed by CYP3A4, BFBFC may be useful fluorescent probed substrate for human hepatic CYP3A4, but compared with 7BQ has only a low rate of metabolism in human liver microsomes.

  DOI：

  10.1080/00498250110043526
• 作为产物：
  描述：

  7-羟基喹啉 、 溴甲苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以33%的产率得到7-苄氧基喹啉
  参考文献：
  名称：

  杂环药物抑制细胞色素 P450 3A4 的动力学定义了一般的顺序多步骤结合过程。

  摘要：

  细胞色素P450（P450）3A4是参与药物代谢最重要的酶，也可以氧化多种类固醇。这种酶也参与药代动力学药物相互作用的一半，但在许多情况下，P450 3A4 抑制的确切机制的细节仍不清楚。酮康唑、克霉唑、利托那韦、茚地那韦和伊曲康唑是强抑制剂；对模型底物 7-苯甲酰喹啉逆转抑制的动力学分析显示，在一些情况下存在滞后期，这与 P450 3A4 抑制剂复合物的多种结构一致。当在 7-苯甲酰喹啉 O-脱苄基反应中将抑制剂添加到 P450 3A4 时，观察到抑制开始的滞后，并且利托那韦和茚地那韦对睾酮 6β-羟基化的抑制也观察到类似的模式。与抑制剂混合后，P450 3A4 显示出快速结合，根据至少部分高自旋铁特征的光谱位移判断，随后较慢地转化为低自旋铁-氮络合物。这些变化可以通过两种中间复合物来最好地描述，一种是部分高自旋形式，第二种是另一种中间体，半衰期为数秒。动力学可以在一个系统中进行建模，该

  DOI：

  10.1074/jbc.ra120.016855

文献信息

• [EN] A PRODRUG OF 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE<br/>[FR] PROMÉDICAMENT DE LA 1,1'-(1,6-DIOXO-1,6-HEXANEDIYL)BIS-D-PROLINE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2015165833A1

  公开（公告）日：2015-11-05

  The present invention relates to the compound (2R,2'R)-bis(((((tetrahydro-2H-pyran- 4-yl)oxy)carbonyl)oxy)methyl) 1,1'-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.

  本发明涉及化合物(2R,2'R)-双((((四氢-2H-吡喃-4-基)氧基)羰基)氧基)甲基)1,1'-己二酰基双(吡咯烷-2-羧酸酯)，包括该化合物的药物组合物以及将其用于治疗血清淀粉样蛋白P成分(SAP)耗竭有益的疾病或疾病的用途，包括淀粉样变性病、阿尔茨海默病、2型糖尿病和骨关节炎。
• [EN] PIPERAZINE DERIVATIVE RENIN INHIBITORS<br/>[FR] DERIVES DE PIPERAZINE AGISSANT COMME INHIBITEURS DE LA RENINE
  申请人：WARNER LAMBERT CO

  公开号：WO2004089915A1

  公开（公告）日：2004-10-21

  Disclosed are piperazine derivatives, their manufacture and use as inhibitors of renin. Formula (I):

  揭示了哌嗪衍生物，它们的制备以及作为肾素抑制剂的用途。化学式（I）：
• NOVEL NON-FLUORESCENT RHODAMINES
  申请人：THE UNIVERSITY OF TOKYO

  公开号：US20210087160A1

  公开（公告）日：2021-03-25

  A novel non-fluorescent rhodamine dye forms a twisted intramolecular charge transfer state. A substituent that causes steric hindrance is introduced at an ortho position of a dimethylamino group on the xanthene ring of tetramethylrhodamine, which is a general rhodamine that exhibits strong fluorescence, and a certain amount of twist is imparted in a ground state. As a result, the formation of the twisted intramolecular charge transfer state is promoted in the excited state and non-fluorescence is exhibited.

  一种新型的非荧光罗丹明染料形成了扭曲的分子内电荷转移态。在四甲基罗丹明的黄色素环上的二甲胺基团的邻位引入了引起立体位阻的取代基，四甲基罗丹明是一种表现出强荧光的通用罗丹明，在基态中赋予了一定程度的扭曲。因此，在激发态中促进了扭曲的分子内电荷转移态的形成，并表现出非荧光性。
• [EN] SMALL-MOLECULE NADPH OXIDASE 2 INHIBITORS<br/>[FR] INHIBITEURS DE NADPH OXYDASE 2 À PETITE MOLÉCULE
  申请人：UNIV COPENHAGEN

  公开号：WO2021105497A1

  公开（公告）日：2021-06-03

  The invention provides compounds of Formula (II) which comprise two terminal 2-aminoquinoline moieties. They are novel and potent inhibitors of the p47phox-p22phox protein-protein interaction that can inhibit the assembly and thus activation of the multisubunit and superoxide-generating NADPH oxidase 2 complex. The compounds are therapeutically relevant as they can reduce cell damage in diseases where NADPH oxidase 2 is a major contributor to generation of reactive oxygen species (ROS) and oxidative stress.

  该发明提供了公式（II）的化合物，其中包括两个末端的2-氨基喹啉基团。它们是新颖且有效的 p47phox-p22phox 蛋白质相互作用抑制剂，可以抑制多亚基和产生超氧化物的 NADPH 氧化酶 2 复合物的组装和激活。这些化合物在治疗上具有重要意义，因为它们可以减少 NADPH 氧化酶 2 在产生活性氧物种（ROS）和氧化应激中起主要作用的疾病中的细胞损伤。
• Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis
  申请人：——

  公开号：US20030236227A1

  公开（公告）日：2003-12-25

  The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, thiazolidinedione analogs that have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds that have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester-containing thiazolidinedione analogs are also taught.

  该发明提供了在治疗2型糖尿病中有用的药物化合物。这些化合物具有优势，因为它们可以被代谢药物解毒系统迅速代谢。特别地，设计了包含酯基的噻唑烷二酮类似物的化合物。该发明还涉及治疗疾病的方法，如糖尿病，包括给予经设计为能够被血清或细胞内酯酶代谢的化合物的治疗有效组合物。还教授了含酯基的噻唑烷二酮类似物的药物组合物。