(-)-4-Hydroxypropranolol | 76792-96-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (-)-4-Hydroxypropranolol
• 英文别名: 4-[(2S)-2-hydroxy-3-(propan-2-ylamino)propoxy]naphthalen-1-ol
• CAS: 76792-96-6
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: CWEPACWBWIOYID-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-4-Hydroxypropranolol 、 (R)-(+)-1-苯乙基异氰酸酯 生成 1-[(2S)-2-hydroxy-3-(4-hydroxynaphthalen-1-yl)oxypropyl]-3-[(1R)-1-phenylethyl]-1-propan-2-ylurea
  参考文献：
  名称：

  SCHAEFER, HANS G.;SPAHN, HILDEGARD;LOPEZ, LARRY M.;DERENDORF, HARTMUT, J. CHROMATOGR. BIOMED. APPL., 527,(1990) N, C. 351-359

  摘要：

  DOI：
• 作为产物：
  描述：

  [(2S)-1-(4-hydroxynaphthalen-1-yl)oxy-3-(propan-2-ylamino)propan-2-yl] hydrogen sulfate 生成 (-)-4-Hydroxypropranolol
  参考文献：
  名称：

  SCHAEFER, HANS G.;SPAHN, HILDEGARD;LOPEZ, LARRY M.;DERENDORF, HARTMUT, J. CHROMATOGR. BIOMED. APPL., 527,(1990) N, C. 351-359

  摘要：

  DOI：

文献信息

• Integrated photocatalytic micropillar nanoreactor electrospray ionization chip for mimicking phase I metabolic reactions
  作者：Teemu Nissilä、Lauri Sainiemi、Mika-Matti Karikko、Marianna Kemell、Mikko Ritala、Sami Franssila、Risto Kostiainen、Raimo A. Ketola

  DOI：10.1039/c0lc00689k

  日期：——

  We developed a nanoreactor chip based system to mimic phase I metabolic reactions of small organic compounds. The microchip, made of silicon, has an anatase-phase titanium dioxide (TiO2) nanolayer coating for photocatalysis and an integrated electrospray ionization (ESI) tip for direct mass spectrometric (MS) analysis. This novel method for mimicking phase I metabolic reactions uses an on-chip TiO2-nanolayer and an external UV-lamp to induce photocatalyzed chemical reactions of drug compounds in aqueous solutions. The reactions of selected test compounds (verapamil, metoprolol, propranolol, lidocaine, 2-acetamidofluorene, and S-methylthiopurine) produced mostly the same main products as phase I metabolic reactions induced by human liver microsomes, rat hepatocytes, or cytochrome P enzymes, showing hydroxylation, dehydrogenation, and dealkylations as the main photocatalytic reactions. With this method it is possible to detect reactive and toxic products (mimicking reactive metabolites) due to the absence of biological matrices and an immediate analysis. The method used is sensitive: only 20–40 pmol (1–10 ng) of a substrate was needed for the experiment, thus it provides an inexpensive method for screening possible metabolites of new drug candidates. Due to small dimensions of the microchip, diffusion lengths are suitable for the high reaction rates, thus providing a rapid analysis as the reaction products can be detected and identified directly after the photoinduced reactions have occurred. The method shows a similar performance to that of electrochemistry, a commonly used technique for mimicking phase I metabolism.

  我们开发了一种基于纳米反应器芯片的系统，用于模拟小型有机化合物的第一阶段代谢反应。这种微芯片由硅制成，具有锐钛矿相二氧化钛（TiO2）纳米层涂层，用于光催化；集成电喷雾离子化（ESI）尖端，用于直接质谱（MS）分析。这种模拟第一阶段代谢反应的新方法使用片上二氧化钛纳米层和外部紫外灯来诱导水溶液中药物化合物的光催化化学反应。选定测试化合物（维拉帕米、美托洛尔、普萘洛尔、利多卡因、2-乙酰氨基芴和 S-甲基硫嘌呤）的反应产生的主要产物与人肝微粒体、大鼠肝细胞或细胞色素 P 酶诱导的 I 期代谢反应基本相同，显示羟化、脱氢和脱烷基是主要的光催化反应。由于不需要生物基质和即时分析，这种方法可以检测反应性和毒性产物（模拟反应性代谢物）。该方法灵敏度高：实验只需 20-40 pmol（1-10 ng）的底物，因此是筛选新药候选物可能代谢物的廉价方法。由于微芯片尺寸小，扩散长度适合高反应速率，因此可以在光诱导反应发生后直接检测和鉴定反应产物，从而提供快速分析。该方法的性能与模拟第一阶段新陈代谢的常用技术--电化学类似。
• Regio- and stereoselective oxidation of propranolol enantiomers by human CYP2D6, cynomolgus monkey CYP2D17 and marmoset CYP2D19
  作者：Shizuo Narimatsu、Toshiyuki Nakata、Takeshi Shimizudani、Kenjiro Nagaoka、Hironori Nakura、Kazufumi Masuda、Takashi Katsu、Akiko Koeda、Shinsaku Naito、Shigeru Yamano、Atsuro Miyata、Nobumitsu Hanioka

  DOI：10.1016/j.cbi.2010.12.014

  日期：2011.2

  Toxic and pharmacokinetic profiles of drug candidates are evaluated in vivo often using monkeys as experimental animals, and the data obtained are extrapolated to humans. Well understanding physiological properties, including drug-metabolizing enzymes, of monkeys should increase the accuracy of the extrapolation. The present study was performed to compare regio- and stereoselectivity in the oxidation of propranolol (PL), a chiral substrate, by cytochrome P450 2D (CYP2D) enzymes among humans, cynomolgus monkeys and marmosets. Complimentary DNAs encoding human CYP2D6, cynomolgus monkey CYP2D17 and marmoset CYP2D19 were cloned, and their proteins expressed in a yeast cell expression system. The regio- and stereoselective oxidation of PL enantiomers by yeast cell microsomal fractions were compared. In terms of efficiency of expression in the system, the bob-proteins ranked CYP2D6=CYP2D17 >> CYP2D19. This may be caused by the bulky side chain of the amino acid residue at position 119 (leucine for CYP2D19 vs. valine for CYP2D6 and CYP2D17), which can disturb the incorporation of the heme moiety into the active-site cavity. PL enantiomers were oxidized by all of the enzymes mainly into 4-hydroxyproranolol (4-OH-PL), followed by 5-OH-PL and N-desisopropylpropranolol (NDP). In the kinetic analysis, apparent K(m) values were commonly in the mu M range and substrate enantioselectivity of R-PL < S-PL was observed in both K(m) and V values for the formation of the three metabolites from PL enantiomers. The activity to produce NEW tended to be higher for the monkey enzymes, particularly CYP2D17, than for the human enzyme. These results indicate that in the oxidation of PL enantiomers by CYP2D enzymes, stereoselectivity is similar but regioselectivity is different between humans and monkeys. (C) 2010 Elsevier Ireland Ltd. All rights reserved.