3-nitro-7H-benzimidazo[2,1-a]benz[de]isoquinolin-7-one | 23986-26-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-nitro-7H-benzimidazo[2,1-a]benz[de]isoquinolin-7-one
• 英文别名: TIM-064；3-Nitro-7H-benzimidazo<2.1a>benz(de)isochinolin-7-on；4(oder 5)-Nitro-1.8-naphthoylen-1'.2'-benzimidazol；4'-Nitro-1,2-naphthoylen-benzimidazol；3-nitro-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one；3-nitro-benzo[de]benz[4,5]imidazo[2,1-a]isoquinolin-7-one；3-Nitro-benzo[de]benz[4,5]imidazo[2,1-a]isochinolin-7-on；3-nitro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one；17-nitro-3,10-diazapentacyclo[10.7.1.02,10.04,9.016,20]icosa-1(20),2,4,6,8,12,14,16,18-nonaen-11-one
• CAS: 23986-26-7
• 化学式: C₁₈H₉N₃O₃
• 分子量: 315.288
• InChiKey: RLOJCIGUFVMNMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-nitro-7H-benzimidazo[2,1-a]benz[de]isoquinolin-7-one 生成 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  Krasowizkii et al., Zhurnal Obshchei Khimii, 1958, vol. 28, p. 2485,2488;engl.Ausg.S.2520,2523

  摘要：

  DOI：
• 作为产物：
  描述：

  4-硝基-1,8-萘醛酸酐 在 邻苯二胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 3-nitro-7H-benzimidazo[2,1-a]benz[de]isoquinolin-7-one
  参考文献：
  名称：

  Development and Characterization of Novel Molecular Probes for Ca²⁺/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609

  摘要：

  (TIM-062)能够抑制离子霉素诱导的HeLa细胞外源表达的CaMKI、CaMKIV和内源性AMPKα的磷酸化，IC50约为0.3μM，并且能够抑制CaMKK异构体介导的COS-7细胞中CaMKIV的磷酸化。因此，TIM-063（而非非活性类似物TIM-062）能够抑制离子霉素诱导的HeLa细胞外源表达的CaMKI、CaMKIV和内源性AMPKα的磷酸化，IC50约为0.3μM，并且能够抑制CaMKK异构体介导的COS-7细胞中CaMKIV的磷酸化。

  DOI：

  10.1021/acs.biochem.0c00149

文献信息

• Pourjavadi, Ali; Marandi, Gholam Bagheri, Journal of Chemical Research - Part S, 2001, # 11, p. 485 - 487
  作者：Pourjavadi, Ali、Marandi, Gholam Bagheri

  DOI：——

  日期：——
• Alexiou; Tyman, Journal of Chemical Research - Part S, 2001, # 2, p. 56 - 58
  作者：Alexiou、Tyman

  DOI：——

  日期：——
• Development and Characterization of Novel Molecular Probes for Ca²⁺/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609
  作者：Satomi Ohtsuka、Yui Ozeki、Moeno Fujiwara、Tomoyuki Miyagawa、Naoki Kanayama、Masaki Magari、Naoya Hatano、Futoshi Suizu、Teruhiko Ishikawa、Hiroshi Tokumitsu

  DOI：10.1021/acs.biochem.0c00149

  日期：2020.5.5

  Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5′AMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKα and CaMKKβ) with a similar potency (Ki = 0.35 μM for CaMKKα, and Ki = 0.2 μM for CaMKKβ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of ∼0.3 μM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases.

  (TIM-062)能够抑制离子霉素诱导的HeLa细胞外源表达的CaMKI、CaMKIV和内源性AMPKα的磷酸化，IC50约为0.3μM，并且能够抑制CaMKK异构体介导的COS-7细胞中CaMKIV的磷酸化。因此，TIM-063（而非非活性类似物TIM-062）能够抑制离子霉素诱导的HeLa细胞外源表达的CaMKI、CaMKIV和内源性AMPKα的磷酸化，IC50约为0.3μM，并且能够抑制CaMKK异构体介导的COS-7细胞中CaMKIV的磷酸化。
• Krasowizkii et al., Zhurnal Obshchei Khimii, 1958, vol. 28, p. 2485,2488;engl.Ausg.S.2520,2523
  作者：Krasowizkii et al.

  DOI：——

  日期：——