N-(4-((2-(2-(naphthalen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide | 1022305-60-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(4-((2-(2-(naphthalen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide
• 英文别名: N-[2-[[4-[[6-(Trifluoromethyl)-3-pyridyl]carbonylamino]piperidine-4-yl]carbonylamino]ethyl]naphthalene-1-acetamide；N-[4-[2-[(2-naphthalen-1-ylacetyl)amino]ethylcarbamoyl]piperidin-4-yl]-6-(trifluoromethyl)pyridine-3-carboxamide
• CAS: 1022305-60-7
• 化学式: C₂₇H₂₈F₃N₅O₃
• 分子量: 527.546
• InChiKey: CJGCBUSLZZJIJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-BOC-4-氨基-4-羧酸哌啶 在 哌啶 、 sodium carbonate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.5h， 生成 N-(4-((2-(2-(naphthalen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide
  参考文献：
  名称：

  Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor

  摘要：

  VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 mu M and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against 1(562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 mu M. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 mu M. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.026

文献信息

• Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor
  作者：Feng Jin、Dan Gao、Qin Wu、Feng Liu、Yuzong Chen、Chunyan Tan、Yuyang Jiang

  DOI：10.1016/j.bmc.2013.07.026

  日期：2013.9

  VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 mu M and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against 1(562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 mu M. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 mu M. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.