2-Hydroxytacrine | 130073-98-2

• 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
• 英文名称: 2-Hydroxytacrine
• 英文别名: 9-Amino-1,2,3,4-tetrahydroacridin-2-ol
• CAS: 130073-98-2
• 化学式: C₁₃H₁₄N₂O
• 分子量: 214.267
• InChiKey: PYCYYSWVRAEADT-UHFFFAOYSA-N

物化性质

• 沸点：
  470.2±45.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)
• 保留指数：
  2130

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  59.1
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

2-羟基他克林是已知的人体他克林的代谢物。

2-Hydroxytacrine is a known human metabolite of tacrine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  2-Hydroxytacrine 以 乙醚 、 甲烷 、 N,N-二甲基甲酰胺二甲基缩醛 为溶剂， 生成 2-Hydroxy-N-(dimethylaminomethylene)-1,2,3,4-tetrahydro-9-acridinamine
  参考文献：
  名称：

  Hydroxy-1,2,3,4-tetrahydroaminoacridines, a process for their preparation and their use as medicaments

  摘要：

  公开号：

  EP0369388B1
• 作为产物：
  描述：

  1,4-环己二酮单乙二醇缩酮 在 盐酸 、 甲醇 、 氢氧化钾 、 sodium tetrahydroborate 、 氨 、 溴 作用下， 以 甲醇 、 乙二醇 为溶剂， 反应 9.33h， 生成 2-Hydroxytacrine
  参考文献：
  名称：

  9-氨基-，9-氨基甲基-1,2,3,4-四氢-和1,2,3,4,5,6,7,8-八氢ac啶衍生物的合成

  摘要：

  本文描述了9-氨基-2-和4-羟基-和2,4-二羟基-1,2,3,4-四氢-啶2和9-氨基甲基-1,2,3,4-的合成从相应的9-羧酰胺基衍生物开始的四氢和1,2,3,4,5,6,7,8-八氢ac啶3。还报道了一种新的合成途径，可合成9-氨基-2-羟基a啶二酮9。

  DOI：

  10.1002/jhet.5570340604

文献信息

• Simultaneous Determination of Tacrine and 1‐Hydroxy‐, 2‐Hydroxy‐, and 4‐Hydroxytacrine in Human Plasma by High‐Performance Liquid Chromatography with Fluorescence Detection
  作者：David B. Haughey、Patricia M. Klockowski、Mary S. Collis、Richard R. Brown、Paul H. Siedlik、Colleen A. McNaney、Linda Balogh

  DOI：10.1002/jps.2600831113

  日期：1994.11

  An analytical method was developed for the simultaneous reversed-phase (cyano) high-performance liquid chromatographic determination with fluorescence detection of tacrine and 1-hydroxy-, 2-hydroxy-, and 4-hydroxytacrine in human plasma. Alkalinized human plasma samples were extracted with a mixture of chloroform/l-propanol (90:10, v/v). Extraction recoveries generally ranged from 68% to 83% for all

  开发了一种分析方法，用于同时反相（氰基）高效液相色谱测定，并通过荧光检测人血浆中的他克林和1-羟基，2-羟基和4-羟基他克林。用氯仿/ 1-丙醇（90：10，v / v）的混合物提取碱化的人血浆样品。对于所有四种化合物，提取回收率通常在68％至83％的范围内，并且在所检查的范围内似乎与浓度无关。在以下范围内构建校正曲线：他克林（THA）和4-羟基他克林（4-OH-THA）为0.5-30.0 ng / mL，2-羟基他克林（2-OH-THA）为1.0-30.0 ng / mL， 1-羟基他克林（1-OH-THA）的浓度为0.925-46.2 ng / mL。验证期间分析的质量控制样品的测定内和测定间精密度（RSD）≤11.8％和< 或分别为9.28％。对于所有四种化合物，在验证过程中分析的质量控制样品的测定内和测定间准确度（RE）分别在14.1％至-7.5％和12.1％至-3.33％之间。基
• Metabolic disposition of tacrine in primary suspensions of rat hepatocyte and in single-pass perfused liver:<i>in vitro/in vivo</i>comparisons
  作者：M. Kukan、Š. Bezek、W. F. Pool、T. F. Woolf

  DOI：10.3109/00498259409038670

  日期：1994.1

  1. Incubations of tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate, THA) with a primary suspension of rat hepatocytes for 2 min resulted in formation of the l-hydroxy derivative as the major metabolite with smaller amounts of the 2- and 4-hydroxy metabolites.2. Apparent V-max and K-m for THA metabolism were 12.4 +/- 3.3 nmol/min/g liver and 0.98 +/- 0.34 mu M respectively.3. Incubations of THA for longer time-periods (> 10 min) resulted in irreversible binding of THA-derived radioactivity to hepatocellular protein. The apparent maximal rate of irreversible binding (B-max) was 76.7 +/- 30.5 pmol equivalents bound/h/mg cell protein, whereas the apparent K-b for binding was 2.8 +/- 1.4 mu M.4. The kinetic parameters, V-max and K-m, were used to predict steady-state extraction ratios (ER(ss)) for various THA input concentrations (C-in) in single-pass perfused rat liver. At low input concentrations (0.72-0.85 mu M; C-in < K-m), ER(ss) of THA was approximately 1. For higher C-in (14.05, 20.72, 20.88 mu M; C-in, much greater than K-m), the calculated ER(ss) was markedly decreased with 0.300, 0.296 and 0.261, respectively.5. The intrinsic clearance of THA (Cl-i) estimated from in vitro hepatocyte data was 6.7 ml/min/g liver while the apparent oral THA clearance (Cl-oral) calculated from in vivo rat data was 6.6 ml/min/g liver.
• Hydroxy-1,2,3,4-tetrahydroaminoacridines, a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0369388B1

  公开（公告）日：1993-05-19
• Synthesis of 9-amino-, 9-aminomethyl-1,2,3,4-tetrahydro- and 1,2,3,4,5,6,7,8-octahydroacridine derivatives
  作者：Maria Rosaria Del Giudice、Anna Borioni、Carlo Mustazza、Franco Gatta

  DOI：10.1002/jhet.5570340604

  日期：1997.11

  This paper describes the synthesis of 9-amino-2- and 4-hydroxy- and 2,4-dihydroxy-1,2,3,4-tetrahydro-acridines 2 and of 9-aminomethyl-1,2,3,4-tetrahydro- and 1,2,3,4,5,6,7,8-octahydroacridines 3 starting from the corresponding 9-carboxamido derivatives. A new synthetical pathway to 9-amino-2-hydroxyacri-dine 9 is also reported.

  本文描述了9-氨基-2-和4-羟基-和2,4-二羟基-1,2,3,4-四氢-啶2和9-氨基甲基-1,2,3,4-的合成从相应的9-羧酰胺基衍生物开始的四氢和1,2,3,4,5,6,7,8-八氢ac啶3。还报道了一种新的合成途径，可合成9-氨基-2-羟基a啶二酮9。