5,6-dihydro-5,6-dioxo-9-chloro-naphtho[1',2':4,5]imidazo[1,2-a]pyridine | 110178-30-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5,6-dihydro-5,6-dioxo-9-chloro-naphtho[1',2':4,5]imidazo[1,2-a]pyridine
• 英文别名: 9-Chloro-5,6-dihydro-5,6-dioxo-naphtho[1',2':4,5]-imidazo[1,2-a]pyridine；9-Chloronaphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-dione；13-chloro-11,17-diazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(10),2,4,6,12,14,16-heptaene-8,9-dione
• CAS: 110178-30-8
• 化学式: C₁₅H₇ClN₂O₂
• 分子量: 282.686
• InChiKey: VZYGUWNBWRRBMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 2-氨基-5-氯吡啶 以 仲丁醇 为溶剂， 反应 36.0h， 以61%的产率得到5,6-dihydro-5,6-dioxo-9-chloro-naphtho[1',2':4,5]imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity

  摘要：

  Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones (NPDOs), a new type of N-heterocycle-fused o-quinones, have been synthesized. They have been found to be efficient electron-accepting substrates of NADPH-dependent single-electron-transferring P-450R and two-electron transferring NQO1, generating reactive oxygen species (ROS) with a concomitant decrease in NADPH, which is consistent with redox-cycling. The reactivity of NPDOs toward P-450R (in terms of k(cat)/K-m) varied in the range of 10(6)-10(7) M-1 s(-1), while their reduction by NQO1 proceeded much faster, approaching the diffusion control limit (k(cat)/K-m similar to 10(8)-10(9) M-1 s(-1)). NPDOs exhibited relatively high cytotoxic activity against human lung carcinoma (A-549) and breast tumor (MCF-7) cell lines (LC50 = 0.1-8.3 mu M), while promyelocytic leukemia cells (HL-60) were less sensitive to NPDOs (LC50 >= 10 mu M). 3-Nitro-substituted NPDO (11) revealed the highest potency against both A-549 and MCF-7 cell lines, with LC50 of 0.12 +/- 0.03 mu M and 0.28 +/- 0.08 mu M, respectively. Dicoumarol partly suppressed the activity of the compounds against A-594 and MCF-7 cell lines, suggesting that their cytotoxic action might be partially influenced by NQO1-mediated bioreductive activation. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.084

文献信息

• US5981544A
  申请人：——

  公开号：US5981544A

  公开（公告）日：1999-11-09
• Naphtho[1′,2′:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity
  作者：Jonas Šarlauskas、Milda Pečiukaitytė-Alksnė、Lina Misevičienė、Audronė Marozienė、Evelina Polmickaitė、Zita Staniulytė、Narimantas Čėnas、Žilvinas Anusevičius

  DOI：10.1016/j.bmcl.2015.11.084

  日期：2016.1

  Naphtho[1',2':4,5]imidazo[1,2-a]pyridine-5,6-diones (NPDOs), a new type of N-heterocycle-fused o-quinones, have been synthesized. They have been found to be efficient electron-accepting substrates of NADPH-dependent single-electron-transferring P-450R and two-electron transferring NQO1, generating reactive oxygen species (ROS) with a concomitant decrease in NADPH, which is consistent with redox-cycling. The reactivity of NPDOs toward P-450R (in terms of k(cat)/K-m) varied in the range of 10(6)-10(7) M-1 s(-1), while their reduction by NQO1 proceeded much faster, approaching the diffusion control limit (k(cat)/K-m similar to 10(8)-10(9) M-1 s(-1)). NPDOs exhibited relatively high cytotoxic activity against human lung carcinoma (A-549) and breast tumor (MCF-7) cell lines (LC50 = 0.1-8.3 mu M), while promyelocytic leukemia cells (HL-60) were less sensitive to NPDOs (LC50 >= 10 mu M). 3-Nitro-substituted NPDO (11) revealed the highest potency against both A-549 and MCF-7 cell lines, with LC50 of 0.12 +/- 0.03 mu M and 0.28 +/- 0.08 mu M, respectively. Dicoumarol partly suppressed the activity of the compounds against A-594 and MCF-7 cell lines, suggesting that their cytotoxic action might be partially influenced by NQO1-mediated bioreductive activation. (C) 2015 Elsevier Ltd. All rights reserved.