2-[3-nitro-6-(piperazin-1-yl)pyridin-2-yl]benzoic acid ethyl ester | 577795-12-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[3-nitro-6-(piperazin-1-yl)pyridin-2-yl]benzoic acid ethyl ester
• 英文别名: Ethyl 2-(3-nitro-6-piperazin-1-ylpyridin-2-yl)benzoate
• CAS: 577795-12-1
• 化学式: C₁₈H₂₀N₄O₄
• 分子量: 356.381
• InChiKey: KSKUNAICVMOHIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[3-nitro-6-(piperazin-1-yl)pyridin-2-yl]benzoic acid ethyl ester 在 镍 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到2-(piperazin-1-yl)-5,6-dihydrobenzo[c][1,5]naphthyridin-6-one
  参考文献：
  名称：

  Design and Synthesis of Poly ADP-ribose Polymerase-1 Inhibitors. 2. Biological Evaluation of Aza-5[H]-phenanthridin-6-ones as Potent, Aqueous-Soluble Compounds for the Treatment of Ischemic Injuries

  摘要：

  A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphyhyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.

  DOI：

  10.1021/jm030109s
• 作为产物：
  描述：

  2-(5,5-二甲基-1,3,2-二氧硼杂烷-2-基)苯甲酸乙酯 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 生成 2-[3-nitro-6-(piperazin-1-yl)pyridin-2-yl]benzoic acid ethyl ester
  参考文献：
  名称：

  Design and Synthesis of Poly ADP-ribose Polymerase-1 Inhibitors. 2. Biological Evaluation of Aza-5[H]-phenanthridin-6-ones as Potent, Aqueous-Soluble Compounds for the Treatment of Ischemic Injuries

  摘要：

  A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphyhyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.

  DOI：

  10.1021/jm030109s

文献信息

• Design and Synthesis of Poly ADP-ribose Polymerase-1 Inhibitors. 2. Biological Evaluation of Aza-5[<i>H</i>]-phenanthridin-6-ones as Potent, Aqueous-Soluble Compounds for the Treatment of Ischemic Injuries
  作者：Dana Ferraris、Yao-Sen Ko、Thomas Pahutski、Rica Pargas Ficco、Larisa Serdyuk、Christina Alemu、Chadwick Bradford、Tiffany Chiou、Randall Hoover、Shirley Huang、Susan Lautar、Shi Liang、Qian Lin、May X.-C Lu、Maria Mooney、Lisa Morgan、Yongzhen Qian、Scott Tran、Lawrence R. Williams、Qi Yi Wu、Jie Zhang、Yinong Zou、Vincent Kalish

  DOI：10.1021/jm030109s

  日期：2003.7.1

  A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors of poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency of the unsubstituted aza-5[H]-phenanthridin-6-ones (i.e., benzonaphyhyridones) was dependent on the position of the nitrogen atom within the core structure. The A ring nitrogen analogues (7-, 8-, and 10-aza-5[H]-phenanthridin-6-ones) were an order of magnitude less potent than C ring nitrogen analogues (1-, 2-, 3-, and 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- and 2-aza-5[H]-phenanthridin-6-one prompted structure-activity relationships to be established for several 2- and 3-substituted 1-aza-5[H]-phenanthridin-6-ones. The 2-substituted 1-aza-5[H]-phenanthridin-6-ones were designed to improve the solubility and pharmacokinetic profiles for this series of PARP-1 inhibitors. Most importantly, three compounds from this series demonstrated statistically significant protective effects in rat models of stroke and heart ischemia.