6,7-Dimethoxy-1-tert-butyl-1,2,3,4-tetrahydro-isochinolin | 2859-19-0

• 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: 6,7-Dimethoxy-1-tert-butyl-1,2,3,4-tetrahydro-isochinolin
• 英文别名: 1-Tert-butyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• CAS: 2859-19-0
• 化学式: C₁₅H₂₃NO₂
• mdl: MFCD09887048
• 分子量: 249.353
• InChiKey: FOAHVIKIRZCFDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-3-tert-butoxycarbonylamino-4-((S)-2-cyano-pyrrolidin-1-yl)-4-oxo-butyric acid 、 6,7-Dimethoxy-1-tert-butyl-1,2,3,4-tetrahydro-isochinolin 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 [(S)-3-(1-tert-Butyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1-((S)-2-cyano-pyrrolidine-1-carbonyl)-3-oxo-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors

  摘要：

  To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine with P2-site 4-substituted glutamic acid derivatives and tested their activities against DPP-IV, DPP8, and DPP-II. Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II. From structure-activity relationship studies, we speculate that the S2 site of DPP8 might be similar to that of DPP-IV, while DPP-IV inhibitor with N-substituted glycine in the P2 site and/or with a moiety involving in hydrophobic interaction with the side chain of Phe357 might provide a better selectivity for DPP-IV over DPP8. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.051
• 作为产物：
  描述：

  N-<2-(3,4-Dimethoxyphenyl)-ethyl>-2,2-dimethylpropionsaeureamid 在 乙醇 、 铂 、 三氯氧磷 、 苯 作用下， 生成 6,7-Dimethoxy-1-tert-butyl-1,2,3,4-tetrahydro-isochinolin
  参考文献：
  名称：

  Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines¹

  摘要：

  DOI：

  10.1021/ja01125a051

文献信息

• Exploration of 2-((Pyridin-4-ylmethyl)amino)nicotinamide Derivatives as Potent Reversal Agents against P-Glycoprotein-Mediated Multidrug Resistance
  作者：Qianqian Qiu、Wei Shi、Zheng Li、Bo Zhang、Miaobo Pan、Jian Cui、Yuxuan Dai、Wenlong Huang、Hai Qian

  DOI：10.1021/acs.jmedchem.6b01879

  日期：2017.4.13

  broad spectrum of unrelated chemotherapeutic drugs in structure and function, leading to chemotherapy failure. A series of 2-((pyridin-4-ylmethyl)amino)nicotinamide derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance (MDR) were designed and synthesized. The majority of target compounds displayed great reversal potency, especially 9n. In-depth studies demonstrated 9n

  ATP结合盒（ABC）转运蛋白的过表达，如ABCB1，通常称为P-糖蛋白（P-gp），在结构和功能上引发了广泛的无关化疗药物的主动流出，从而导致化疗失败。设计并合成了一系列2-（（吡啶-4-基甲基）氨基）烟酰胺衍生物，作为对抗P-糖蛋白介导的多药耐药性（MDR）的有效逆转剂。大多数目标化合物显示出很大的逆转能力，尤其是9n。深入研究表明，9n在逆转K562 / A02细胞中对阿霉素（ADM）的耐药性方面具有很高的效力（EC 50 = 119.6±6.9 nM），低细胞毒性和较长的持续时间（> 24小时）。9n还改善了与MDR相关的其他细胞毒性剂的作用，增加了ADM的积累，中断了P-gp介导的Rh123外排功能，并抑制了K562 / A02 MDR细胞中的P-gp ATPase活性。Western印迹分析表明MDR逆转9n不是由于蛋白质表达的降低。此外，CYP3A4的作用不受9n的影响，避免
• o-Benzenedisulfonimide as a reusable acid catalyst for an easy, efficient, and green synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines through Pictet–Spengler reaction
  作者：Margherita Barbero、Stefano Bazzi、Silvano Cadamuro、Stefano Dughera

  DOI：10.1016/j.tetlet.2010.09.149

  日期：2010.12

  tetrahydro-β-carbolines, using the Pictet–Spengler reaction, was carried out in the presence of a catalytic amount of o-benzenedisulfonimide, which worked as a Brønsted acid organocatalyst. The reaction conditions were mild and green and good target product yields were achieved. The catalyst was easily recovered and purified, ready to be used in further reactions with economic and ecological advantages.

  使用Pictet-Spengler反应，在催化量的邻苯二磺酰亚胺的存在下进行四氢异喹啉和四氢β-咔啉的合成，该邻苯二磺酰亚胺用作布朗斯台德酸有机催化剂。反应条件温和绿色，并获得了良好的目标产物收率。该催化剂易于回收和纯化，准备用于经济和生态优势的进一步反应中。
• 1-alkyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline compounds
  申请人：SMITH KLINE FRENCH LAB

  公开号：US02663709A1

  公开（公告）日：1953-12-22
• Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors
  作者：I-Lin Lu、Shiow-Ju Lee、Hsu Tsu、Su-Ying Wu、Kuo-His Kao、Chia-Hui Chien、Ying-Ying Chang、Yuan-Shou Chen、Jai-Hong Cheng、Chung-Nien Chang、Tung-Wei Chen、Sheng-Ping Chang、Xin Chen、Weir-Torn Jiaang

  DOI：10.1016/j.bmcl.2005.04.051

  日期：2005.7

  To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine with P2-site 4-substituted glutamic acid derivatives and tested their activities against DPP-IV, DPP8, and DPP-II. Analogues that incorporated a bulky substituent at the first carbon position of benzylamine or isoquinoline showed over 30-fold selectivity for DPP-IV over both DPP8 and DPP-II. From structure-activity relationship studies, we speculate that the S2 site of DPP8 might be similar to that of DPP-IV, while DPP-IV inhibitor with N-substituted glycine in the P2 site and/or with a moiety involving in hydrophobic interaction with the side chain of Phe357 might provide a better selectivity for DPP-IV over DPP8. (c) 2005 Elsevier Ltd. All rights reserved.
• Tetrahydroisoquinolines. I. 1-Alkyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines¹
  作者：P. N. Craig、F. P. Nabenhauer、P. M. Williams、E. Macko、J. Toner

  DOI：10.1021/ja01125a051

  日期：1952.3