N-cyclohexyl-4-(6-methoxy-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine | 1428959-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-cyclohexyl-4-(6-methoxy-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine
• 英文别名: N-cyclohexyl-4-(6-methoxy-2-naphthalen-2-ylbenzimidazol-1-yl)pyrimidin-2-amine
• CAS: 1428959-02-7
• 化学式: C₂₈H₂₇N₅O
• 分子量: 449.555
• InChiKey: QJPWQJPSTPILRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-cyclohexyl-4-(6-methoxy-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以38%的产率得到1-(2-(cyclohexylamino)pyrimidin-4-yl)-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-6-ol
  参考文献：
  名称：

  Discovery of a Potent and Selective JNK3 Inhibitor with Neuroprotective Effect Against Amyloid β-Induced Neurotoxicity in Primary Rat Neurons

  摘要：

  作为MAPK家族的成员，c-Jun-N末端激酶（JNKs）调节细胞凋亡的生物过程。特别是，JNK3亚型在大脑中以高水平明确表达，并参与神经退行性疾病如阿尔茨海默病（AD）和帕金森病（PD）的发病机制。在这项研究中，我们制备了一系列五种6-二羟基-1H-苯并[d]咪唑作为JNK3抑制剂，发现它们具有作为神经保护剂的潜力。在之前的引物骨架基础上，苯并咪唑基团经过各种芳基和羟基修饰，得到的化合物表现出改进的JNK3抑制活性和选择性。在合成的37个类似物中，（S）-环丙基（3-（（4-（2-（2,3-二氢苯并[b][1,4]二氧杂环己-6-基）-5,6-二羟基-1H-苯并[d]咪唑-1-基）嘧啶-2-基）氨基）哌啶-1-基）甲酮（35b）表现出最高的JNK3抑制作用（IC50 = 9.7 nM），以及对Aβ诱导的神经元细胞死亡的神经保护作用。作为蛋白激酶抑制剂，它还显示出对其他蛋白激酶，包括JNK1（＞1000倍）和JNK2（-10倍）亚型的优异选择性。

  DOI：

  10.3390/ijms222011084
• 作为产物：
  描述：

  4-methoxyphenylene-1,2-diamine dihydrochloride 在 tris-(dibenzylideneacetone)dipalladium(0) 、 BINAP 、 三乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 19.5h， 生成 N-cyclohexyl-4-(6-methoxy-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1 H -benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

  摘要：

  1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of K-d using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 mu M-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (K-d = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 mu M) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.021

文献信息

• JNK 저해 활성을 갖는 신규한 벤즈이미다졸 유도체 및 이의 용도
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus 한양대학교 에리카산학협력단(120120008551) Corp. No ▼ 131471-0017977BRN ▼134-82-10205

  公开号：KR101840674B1

  公开（公告）日：2018-03-21

  본 발명은 JNK (C-Jun N-terminal kinase) 저해 활성을 갖는 신규한 벤즈이미다졸 유도체 및 이의 용도에 관한 것이다. 본 발명에 따른 신규 벤즈이미다졸유도체 또는 이의 약학적으로 허용가능한 염은 JNK 3 (c-Jun N-terminal kinase 3)에 대한 우수한 저해 활성을 나타내는바, 퇴행성 뇌신경계 질환의 예방 또는 치료에 있어서, 보다 근본적으로 접근하여 타겟 치료할 수 있을 것으로 기대된다.

  本发明涉及具有JNK（C-Jun N末端激酶）抑制活性的新型苯并咪唑衍生物及其用途。根据本发明，新型苯并咪唑衍生物或其药学上可接受的盐表现出对JNK 3（C-Jun N末端激酶3）的优异抑制活性，预计可以更根本地针对治疗退行性脑神经系统疾病进行靶向治疗。
• Benzimidazole derivative having JNK inhibitory activity and use thereof
  申请人：INDUSTRY-UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY ERICA CAMPUS

  公开号：US10781201B2

  公开（公告）日：2020-09-22

  The present invention relates to a novel benzimidazole derivative having JNK (C-Jun N-terminal kinase) inhibitory activity and use thereof. The novel benzimidazole derivative or a pharmaceutically acceptable salt thereof according to the present invention exhibits excellent inhibitory activity against c-Jun N-terminal kinase 3(JNK 3), and thus it is expected that target therapy can be attained through a more fundamental approach in the prevention or treatment of degenerative brain-nerve system disease.

  本发明涉及一种具有JNK（C-Jun N-末端激酶）抑制活性的新型苯并咪唑衍生物及其用途。根据本发明的新型苯并咪唑衍生物或其药学上可接受的盐对C-Jun N-末端激酶3（JNK 3）具有极佳的抑制活性，因此有望通过更根本的方法实现靶向治疗，预防或治疗退行性脑神经系统疾病。
• NOVEL BENZIMIDAZOLE DERIVATIVE HAVING JNK INHIBITORY ACTIVITY AND USE THEREOF
  申请人：INDUSTRY-UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY ERICA CAMPUS

  公开号：US20200039959A1

  公开（公告）日：2020-02-06

  The present invention relates to a novel benzimidazole derivative having JNK (C-Jun N-terminal kinase) inhibitory activity and use thereof. The novel benzimidazole derivative or a pharmaceutically acceptable salt thereof according to the present invention exhibits excellent inhibitory activity against c-Jun N-terminal kinase 3(JNK 3), and thus it is expected that target therapy can be attained through a more fundamental approach in the prevention or treatment of degenerative brain-nerve system disease.