4-氨基-1,2,3,4-四氢-1-异喹啉酮 | 124328-39-8

• 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
• 中文名称: 4-氨基-1,2,3,4-四氢-1-异喹啉酮
• 英文名称: amino-4 tetrahydro-1,2,3,4 isoquinolone-1
• 英文别名: 4-Amino-3,4-dihydroisoquinolin-1(2H)-one；4-amino-3,4-dihydro-2H-isoquinolin-1-one
• CAS: 124328-39-8
• 化学式: C₉H₁₀N₂O
• mdl: MFCD12024781
• 分子量: 162.191
• InChiKey: XPRLKELCMYQPJW-UHFFFAOYSA-N

物化性质

• 沸点：
  395.6±42.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-[(3,4-二氢-4-氧代-1-酞嗪基)甲基]-苯甲酸 、 4-氨基-1,2,3,4-四氢-1-异喹啉酮 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以61%的产率得到N-(1-oxo-3,4-dihydro-2H-isoquinolin-4-yl)-3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Benzo[de][1,7]naphthyridin-7(8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors

  摘要：

  A series of benzo[de][1,7]naphthyridin-7(8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors. The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1(2H)-one framework and showing remarkably high PARP1 inhibitory activity (0.31 nM) but only moderate potency in the cell. Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0.26 nM). Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells. Significant potentiation on the cytotoxicity of Temozolomide was also observed. The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.

  DOI：

  10.1021/jm301825t
• 作为产物：
  描述：

  trifluoroacetylamino-4 indanone-1 在 sodium azide 、 三氟乙酸 、 barium(II) hydroxide 作用下， 以 甲醇 为溶剂， 反应 84.0h， 生成 4-氨基-1,2,3,4-四氢-1-异喹啉酮
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Benzo[de][1,7]naphthyridin-7(8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors

  摘要：

  A series of benzo[de][1,7]naphthyridin-7(8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors. The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1(2H)-one framework and showing remarkably high PARP1 inhibitory activity (0.31 nM) but only moderate potency in the cell. Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0.26 nM). Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells. Significant potentiation on the cytotoxicity of Temozolomide was also observed. The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.

  DOI：

  10.1021/jm301825t

文献信息

• Dallemagne, P.; Tembo, O.; Rault, S., Bulletin de la Societe Chimique de France, 1989, # 1, p. 98 - 103
  作者：Dallemagne, P.、Tembo, O.、Rault, S.、Robba, M.

  DOI：——

  日期：——
• DALLEMAGNE, P.;TEMBO, O.;RAULT, S.;ROBBA, M., BULL. SOC. CHIM. FR.,(1989) N, C. 98-103
  作者：DALLEMAGNE, P.、TEMBO, O.、RAULT, S.、ROBBA, M.

  DOI：——

  日期：——