N-{4-[2-(7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-4,5-dimethoxy-2-nitrobenzamide | 1251567-64-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-{4-[2-(7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-4,5-dimethoxy-2-nitrobenzamide
• 英文别名: N-{4-[2-(7-hydroxy-6-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethyl]phenyl}-4,5-dimethoxy-2-nitrobenzamide；N-[4-[2-(7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]-4,5-dimethoxy-2-nitrobenzamide
• CAS: 1251567-64-2
• 化学式: C₂₇H₂₉N₃O₇
• 分子量: 507.543
• InChiKey: CBTOWBRPILTBNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-{4-[2-(7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-4,5-dimethoxy-2-nitrobenzamide 在 5% Pd(II)/C(eggshell) 、 甲酸铵 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 quinoline-3-carboxylic acid [2-(4-{2-[7-(2-fluoroethoxy)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethyl}phenylcarbamoyl)-4,5-dimethoxyphenyl]amide
  参考文献：
  名称：

  Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters

  摘要：

  The purpose of this study was to synthesize two new positron emission tomography (PET) probes, N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[F-18]fluoroethoxy-9- oxo-4-acridine carboxamide ([F-18]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[F-18] fluoroethoxy)6- methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethyl}phenylcarbamoyl)-4,5-dimethoxyphenyl] amide ([F-18]4), andtoevaluate the potential of these PET probes for assessing the function of two major drug efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). [F-18]3 and [F-18]4 were synthesized by F-18-alkylation of each O-desmethyl precursor with [F-18]2-fluoroethyl bromide for injection as PET probes. In vitroaccumulation assayshowed that treatmentwith P-gp/BCRPinhibitors (1 and 2) enhanced the intracellular accumulation capacity of P-gp-and BCRP-overexpressing MES-SA/Dx5 cells. In PET studies, the uptake (AUC(brain) ([0-60 min])) of [F-18]3 and [F-18]4 in wild-type mice co-injected with 1 were approximately sevenfold higher than that in wild-typemice, and the uptake of [F-18]3 and [F-18]4 in P-gp/Bcrp knockoutmicewere eightto ninefold higher than that in wild-typemice. The increased uptake of [F-18]3 and [F-18]4 was similar to that of parent compounds([C-11]1 and [C-11]2) previously described, indicating that radioactivity levels in the brain after injection of [F-18] 3 and [F-18]4 are related to the function of drug efflux transporters. Also, these results suggest that the structural difference between parent compounds ([C-11]1 and [C-11]2) and fluoroethyl analogs ([F-18]3 and [F-18]4) do not obviously affect the potency against drug efflux transporters. Inmetabolite analysis of mice, the unchanged form in the brain and plasma at 60 min after co-injection of [F-18]4 plus 1 were higher (95% for brain; 81% for plasma) than that after co-injection of [F-18]3 plus 1. [F-18]4 is a promising PET probe to assess the function of drug efflux transporters. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.004