(S)-2-((1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl)amino)naphthalene-1,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-2-((1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl)amino)naphthalene-1,4-dione
• 英文别名: 2-[[(3S)-1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl]amino]naphthalene-1,4-dione
• 化学式: C₂₅H₂₅N₅O₄
• 分子量: 459.505
• InChiKey: ZLHMTVZLNSBOJW-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-3-Boc-氨基哌啶 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 异戊醇 为溶剂， 130.0 ℃ 、101.33 kPa 条件下， 反应 26.83h， 生成 (S)-2-((1-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperidin-3-yl)amino)naphthalene-1,4-dione
  参考文献：
  名称：

  Quinazoline based α 1 -adrenoreceptor antagonists with potent antiproliferative activity in human prostate cancer cell lines

  摘要：

  New alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists related to prazosin and doxazosin were synthesized by replacing piperazine ring with (S)- or (R)-3-aminopiperidine. Binding studies indicated that the S configuration at the 3-C position of the piperidine ring is crucial for an optimal interaction of the compounds at all three alpha(1)-AR subtypes. Quinazolines 9 and 10, bearing a quinone ring on the lateral chain, exhibited also potent antiproliferative activity in LNCaP androgen-sensitive prostate cancer cell lines, higher than that of doxazosin. Compound 10 increased apoptosis, in terms of DNA fragmentation, without triggering cell necrosis. The prooxidant activity found in compound 10 may underlie its ability to inhibit cell proliferation in synergy with the effect mediated by alpha(1)-AR antagonism. Due to its better biological profile compared to doxazosin for LNCaP cell line, compound 10 might be a valuable lead compound for the design of new prostate antitumor agents. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.05.003

文献信息

• Quinazoline based α 1 -adrenoreceptor antagonists with potent antiproliferative activity in human prostate cancer cell lines
  作者：Valentina Maestri、Andrea Tarozzi、Elena Simoni、Antonio Cilia、Elena Poggesi、Marina Naldi、Benedetta Nicolini、Letizia Pruccoli、Michela Rosini、Anna Minarini

  DOI：10.1016/j.ejmech.2017.05.003

  日期：2017.8

  New alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists related to prazosin and doxazosin were synthesized by replacing piperazine ring with (S)- or (R)-3-aminopiperidine. Binding studies indicated that the S configuration at the 3-C position of the piperidine ring is crucial for an optimal interaction of the compounds at all three alpha(1)-AR subtypes. Quinazolines 9 and 10, bearing a quinone ring on the lateral chain, exhibited also potent antiproliferative activity in LNCaP androgen-sensitive prostate cancer cell lines, higher than that of doxazosin. Compound 10 increased apoptosis, in terms of DNA fragmentation, without triggering cell necrosis. The prooxidant activity found in compound 10 may underlie its ability to inhibit cell proliferation in synergy with the effect mediated by alpha(1)-AR antagonism. Due to its better biological profile compared to doxazosin for LNCaP cell line, compound 10 might be a valuable lead compound for the design of new prostate antitumor agents. (C) 2017 Elsevier Masson SAS. All rights reserved.