2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)-amino]methyl]phenol

• 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: 2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)-amino]methyl]phenol
• 英文别名: 2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)amino]methyl]phenol；2-[(4-Methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)amino]methyl]phenol
• 化学式: C₂₄H₃₃N₃O
• 分子量: 379.546
• InChiKey: BFNPKJDXPRPTIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)-amino]methyl]phenol 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)-amino]methyl]phenol trihydrochloride
  参考文献：
  名称：

  [EN] DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS
  [FR] ANTAGONISTES DIARYLALKYLAMINES DE REV-ERB ET LEUR UTILISATION COMME MÉDICAMENTS

  摘要：

  本发明涉及式（I）的化合物或其药用可接受的盐或溶剂：还揭示了一种包括式（I）化合物的药物组合物，以及它们作为抗增殖和促凋亡剂用于癌症治疗的用途。

  公开号：

  WO2015052283A1
• 作为产物：
  描述：

  1-苯基-1-环戊醇 在 lithium aluminium tetrahydride 、 sodium azide 、 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-[(4-methylpiperazin-1-yl)methyl]-4-[[(1-phenylcyclopentyl)-amino]methyl]phenol
  参考文献：
  名称：

  Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy

  摘要：

  Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERB beta plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentynamino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV-ERB beta and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERB beta and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERB beta antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15-fold greater REV-ERB beta inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells.

  DOI：

  10.1021/acs.jmedchem.5b00511

文献信息

• [EN] DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS<br/>[FR] ANTAGONISTES DIARYLALKYLAMINES DE REV-ERB ET LEUR UTILISATION COMME MÉDICAMENTS
  申请人：FOND ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：WO2015052283A1

  公开（公告）日：2015-04-16

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof : It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.

  本发明涉及式（I）的化合物或其药用可接受的盐或溶剂：还揭示了一种包括式（I）化合物的药物组合物，以及它们作为抗增殖和促凋亡剂用于癌症治疗的用途。
• DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS
  申请人：FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：US20160237057A1

  公开（公告）日：2016-08-18

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.

  本发明涉及式（I）的化合物或其药学上可接受的盐或溶剂：它进一步揭示了包含式（I）化合物的制药组合物以及它们作为抗增殖和促凋亡剂用于癌症治疗的用途。
• US9611245B2
  申请人：——

  公开号：US9611245B2

  公开（公告）日：2017-04-04
• US9949968B2
  申请人：——

  公开号：US9949968B2

  公开（公告）日：2018-04-24
• Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy
  作者：Esther Torrente、Chiara Parodi、Luisa Ercolani、Claudia De Mei、Alessio Ferrari、Rita Scarpelli、Benedetto Grimaldi

  DOI：10.1021/acs.jmedchem.5b00511

  日期：2015.8.13

  Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERB beta plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentynamino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV-ERB beta and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERB beta and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERB beta antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15-fold greater REV-ERB beta inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells.