4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-(4-(2-Methoxyphenyl)piperazin-1-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine；4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[3,4-d]pyrimidine
• 化学式: C₂₂H₂₂N₆O
• 分子量: 386.456
• InChiKey: JFBXEXDZHRGQKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-1-苯基-1H-吡唑并[3,4-d]嘧啶 在 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  新型GLUT抑制剂的鉴定

  摘要：

  使用HTS将1 H-吡唑并[3,4- d ]嘧啶类化合物鉴定为促进葡萄糖转运蛋白1（GLUT1）的非常有效的抑制剂。建立了分子框架每个环系统的广泛结构-活性关系研究（SAR），揭示了必要的结构动机（即，邻甲氧基取代的苯，哌嗪和嘧啶）。对GLUT2的选择性非常好，并且最初的体外和体内药代动力学（PK）研究令人鼓舞。

  DOI：

  10.1016/j.bmcl.2016.02.050

文献信息

• [EN] GLUCOSE TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DU GLUCOSE
  申请人：BAYER PHARMA AG

  公开号：WO2013182612A1

  公开（公告）日：2013-12-12

  The present invention relates to chemical compounds of general formula (I): in which RA, RB, RC, RD, m, and n are as given in the description and in the claims, and which effectively and selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及通式(I)的化合物：其中RA、RB、RC、RD、m和n如描述和权利要求中所述，并且有效地且选择性地抑制葡萄糖转运蛋白1（GLUT1），以及制备该化合物的方法，包括含有该化合物的药物组合物和药物组合物，以及利用该化合物制造用于治疗或预防疾病的药物组合物的用途，以及在制备该化合物中有用的中间体化合物。
• 4-Substituted-1-phenyl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity
  作者：Safinaz E.-S. Abbas、Enayat I. Aly、Fadi M. Awadallah、Walaa R. Mahmoud

  DOI：10.1111/cbdd.12451

  日期：2015.5

  Four series of some 4‐substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine derivatives 5a–f, 6a–f, 8a–f, and 9a–f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF‐7) and lung (A‐549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR‐TK inhibitory activity where they revealed 41–91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP‐binding site of EGFR‐TK demonstrated their binding mode where H‐bonding interaction with Met793 through N1 of pyrimidine or N2 of pyrazole was observed.