tert-butyl 6-methoxy-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate | 1313873-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: tert-butyl 6-methoxy-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate
• CAS: 1313873-27-6
• 化学式: C₂₂H₃₅NO₇
• 分子量: 425.522
• InChiKey: JGVTYTOKNUINEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  30.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  75.69
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-methoxy-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate 在 盐酸 、 水 、 potassium carbonate 作用下， 以 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 生成 6-methoxy-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2-(4-nitrophenethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2)

  摘要：

  Aiming at structural optimization of potent and selective ABCG2 inhibitors, such as UR-ME22-1, from our laboratory, an efficient solid phase synthesis was developed to get convenient access to this class of compounds. 7-Carboxyisatoic anhydride was attached to Wang resin to give resin bound 2-aminoterephthalic acid. Acylation with quinoline-2- or -6-carbonyl chlorides, coupling with tetrahydroisoquinolinylethylphenylamine derivatives, cleavage of the carboxylic acids from solid support and treatment with trimethylsilydiazomethane gave the corresponding methyl esters. Among these esters highly potent and selective ABCG2 modulators were identified (inhibition of ABCB1 and ABCG2 determined in the calcein-AM and the Hoechst 33342 microplate assay, respectively). Interestingly, compounds bearing triethyleneglycol ether groups at the tetrahydroisoquinoline moiety (UR-COP77, UR-COP78) were comparable to UR-ME22-1 in potency but considerably more efficient (max inhibition 83% and 88% vs 60%, rel. to fumitremorgin c, 100%) These results support the hypothesis that solubility of the new ABCG2 modulators and of the reference compounds tariquidar and elacridar in aqueous media is the efficacy-limiting factor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.094
• 作为产物：
  描述：

  1,2,3,4-四氢-6-甲氧基-7-异羟基喹啉盐酸盐 在 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 tert-butyl 6-methoxy-7-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2)

  摘要：

  Aiming at structural optimization of potent and selective ABCG2 inhibitors, such as UR-ME22-1, from our laboratory, an efficient solid phase synthesis was developed to get convenient access to this class of compounds. 7-Carboxyisatoic anhydride was attached to Wang resin to give resin bound 2-aminoterephthalic acid. Acylation with quinoline-2- or -6-carbonyl chlorides, coupling with tetrahydroisoquinolinylethylphenylamine derivatives, cleavage of the carboxylic acids from solid support and treatment with trimethylsilydiazomethane gave the corresponding methyl esters. Among these esters highly potent and selective ABCG2 modulators were identified (inhibition of ABCB1 and ABCG2 determined in the calcein-AM and the Hoechst 33342 microplate assay, respectively). Interestingly, compounds bearing triethyleneglycol ether groups at the tetrahydroisoquinoline moiety (UR-COP77, UR-COP78) were comparable to UR-ME22-1 in potency but considerably more efficient (max inhibition 83% and 88% vs 60%, rel. to fumitremorgin c, 100%) These results support the hypothesis that solubility of the new ABCG2 modulators and of the reference compounds tariquidar and elacridar in aqueous media is the efficacy-limiting factor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.094

文献信息

• Tariquidar-Related Chalcones and Ketones as ABCG2 Modulators
  作者：Diana Peña-Solórzano、Matthias Scholler、Günther Bernhardt、Armin Buschauer、Burkhard König、Cristian Ochoa-Puentes

  DOI：10.1021/acsmedchemlett.8b00289

  日期：2018.8.9

  ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse anticancer drugs. In order to investigate their role in resistance, potent and selective ABCG2 modulators have been described in the literature. A leading class of modulators are the tariquidar analogues; however, their susceptibility to hydrolysis limits their applicable use. To overcome this, we synthesized a novel series of chalcone- and ketone-based compounds inspired by reported tariquidar analogues. Compounds were characterized and evaluated for their ABCG2 modulatory activity and ABC transporter selectivity. When compared to transporters ABCB1 and ABCC1, the chalcone-based compounds exhibited selectivity for ABCG2, while the ketone-based compounds showed only a slight preference for ABCG2. From the former series, chalcone 16d (UR-DP48) displayed similar activity to the reference fumitremorgin C, both producing comparable maximal effects. The compound exhibited marked antiproliferative activity, while cytotoxicity was less pronounced for the most active compound 17f from the ketone series. Chalcone-containing tariquidar analogues are promising modulators to aid in functional investigations of ABCG2 transporters.