N-{2-[(isoquinoline-5-sulfonyl)amino]ethyl}cyclohexanecarboxamide | 1453814-94-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-{2-[(isoquinoline-5-sulfonyl)amino]ethyl}cyclohexanecarboxamide
• 英文别名: N-[2-(5-isoquinolylsulfonylamino)ethyl]cyclohexanecarboxamide；N-[2-(isoquinolin-5-ylsulfonylamino)ethyl]cyclohexanecarboxamide
• CAS: 1453814-94-2
• 化学式: C₁₈H₂₃N₃O₃S
• 分子量: 361.465
• InChiKey: ITAPYJMORAWSQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  96.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异喹啉-5-磺酰氯盐酸盐 在 碳酸氢钠 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 N-{2-[(isoquinoline-5-sulfonyl)amino]ethyl}cyclohexanecarboxamide
  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

• Synthesis and Structure–Activity relationship of 1-(5-isoquinolinesulfonyl)piperazine analogues as inhibitors of Mycobacterium tuberculosis IMPDH
  作者：Vinayak Singh、Angela Pacitto、Stefano Donini、Davide M. Ferraris、Sándor Boros、Eszter Illyés、Bálint Szokol、Menico Rizzi、Tom L. Blundell、David B. Ascher、Janos Pato、Valerie Mizrahi

  DOI：10.1016/j.ejmech.2019.04.027

  日期：2019.7

  Tuberculosis (TB) is a major infectious disease associated increasingly with drug resistance. Thus, new anti-tubercular agents with novel mechanisms of action are urgently required for the treatment of drug-resistant TB. In prior work, we identified compound 1 (cyclohexyl(4-(isoquinolin-5-ylsulfonyl)piperazin-1-yl)methanone) and showed that its anti-tubercular activity is attributable to inhibition

  结核病（TB）是一种越来越多的与耐药性相关的主要传染病。因此，迫切需要具有新颖作用机制的新抗结核药来治疗耐药性TB。在先前的工作中，我们鉴定了化合物1（环己基（4-（异喹啉-5-基磺酰基）哌嗪-1-基）甲酮），并显示其抗结核活性可归因于肌苷5'-单磷酸脱氢酶（IMPDH）的抑制作用。 ）在结核分枝杆菌中。在本研究中，我们通过在生化和全细胞分析中合成和评估类似物对结核分枝杆菌IMPDH的抑制活性，探索了化合物1周围的构效关系。进行X射线晶体学分析以阐明所选类似物与IMPDH的结合方式。我们确定了环己基的重要性，
• 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.