2-[(4-methylpiperazin-1-yl)methyl]benzaldehyde | 628311-19-3

• 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]benzaldehyde
• 英文别名: 2-[(4-Methylpiperazino)methyl]benzaldehyde
• CAS: 628311-19-3
• 化学式: C₁₃H₁₈N₂O
• 分子量: 218.299
• InChiKey: LMERFIDNODZXKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(4-methylpiperazin-1-yl)methyl]benzaldehyde 、 1-(2-fluorophenyl)cyclopentan amine 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 1-(2-fluorophenyl)-N-[[2-[(4-methylpiperazin-1-yl)methyl]-phenyl]methyl]cyclopentanamine trihydrochloride
  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
• 作为产物：
  描述：

  2-醛基苯甲酸甲酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 2-[(4-methylpiperazin-1-yl)methyl]benzaldehyde
  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

• Amino-functional chalcones
  申请人：Nielsen Feldbaek Simone

  公开号：US20060052600A1

  公开（公告）日：2006-03-09

  The invention provides novel amino-functionalised chalcone derivatives and analogues thereof. Use of the compounds, or compositions comprising them, as pharmaceutically active agents, in particular against bacterial and parasitic infections, is also disclosed. The invention further relates to a method for detecting inhibitory effects against e.g., bacteria, parasites, fungi, and helminths. The chalcones of the invention carry amino substituents and exhibit enhanced biological effects combined with improved metabolic and physicochemical properties, making the compounds useful as drug substances, in particular as antiparasitic, and bacteriocidal agents.

  本发明提供了新型氨基功能化的查尔酮衍生物及其类似物。本发明还揭示了将该化合物或包含其的组合物用作药物活性剂，特别是用于治疗细菌和寄生虫感染。本发明还涉及一种检测抑制细菌、寄生虫、真菌和蠕虫等的方法。本发明的查尔酮具有氨基取代基，具有增强的生物效应和改善的代谢和物理化学性质，使该化合物可用作药物物质，特别是作为抗寄生虫和杀菌剂。
• Diamino-functional chalcones
  申请人：Nielsen Feldbaek Simon

  公开号：US20060235073A1

  公开（公告）日：2006-10-19

  The invention provides novel diamino-functionalised chalcone derivatives and analogues thereof. Use of the compounds, or compositions comprising them, as pharmaceutically active agents, in particular against bacterial and parasitic infections, is also disclosed. The invention further relates to a method for detecting inhibitory effects against e.g., bacteria, parasites, fungi, and helminths. The chalcones of the invention carry amino substituents and exhibit enhanced biological effects combined with improved metabolic and physicochemical properties, making the compounds useful as drug substances, in particular as antiparasitic and bacteriostatic agents.

  本发明提供了新型二氨基官能化查尔酮衍生物及其类似物。本发明还揭示了将这些化合物或包含它们的组合物用作药物活性剂，特别是用于对抗细菌和寄生虫感染。本发明还涉及一种检测抑制对细菌、寄生虫、真菌和蠕虫等的影响的方法。本发明的查尔酮具有氨基取代基，并表现出增强的生物效应和改善的代谢和物理化学性质，使这些化合物在药物物质中有用，特别是作为抗寄生虫和抗菌剂。
• 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。
• AMINO-FUNCTIONAL CHALCONES
  申请人：Lica Pharmaceuticals A/S

  公开号：EP1506157A2

  公开（公告）日：2005-02-16
• DIAMINO-FUNCTIONAL CHALCONES
  申请人：Lica Pharmaceuticals A/S

  公开号：EP1506158A2

  公开（公告）日：2005-02-16