5-amino-3-(thiophen-2-yl)isoquinolin-1-one | 1450605-90-9

• 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
• 英文名称: 5-amino-3-(thiophen-2-yl)isoquinolin-1-one
• 英文别名: 5-amino-3-thiophen-2-yl-2H-isoquinolin-1-one
• CAS: 1450605-90-9
• 化学式: C₁₃H₁₀N₂OS
• 分子量: 242.301
• InChiKey: INTOBQBKQVZYNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(噻吩-2-基)-1,3-丁二酮 在 potassium tert-butylate 、 氨 、 氯化亚锡 、 铜 作用下， 以 乙醇 、 乙二醇甲醚 、 叔丁醇 为溶剂， 反应 24.0h， 生成 5-amino-3-(thiophen-2-yl)isoquinolin-1-one
  参考文献：
  名称：

  One-pot tandem Hurtley–retro-Claisen–cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs

  摘要：

  Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of beta-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins. Treatment with ammonia at high temperature and reduction with tin(II) chloride gave eleven target 3-substituted 5-AIQs, which were all soluble in water (>1% w/ v) as their HCl salts. Most were more potent than 5-AIQ as inhibitors of PARP-1 and of PARP-2 in vitro, the most active being 5-amino-3-methylisoquinolin-1-one (PARP-1: IC50 = 0.23 mu M vs IC50 = 1.6 mu M for 5-AIQ). Some rationalisation of the SAR was achieved through molecular modelling. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.031

文献信息

• One-pot tandem Hurtley–retro-Claisen–cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs
  作者：Esther C.Y. Woon、Peter T. Sunderland、Helen A. Paine、Matthew D. Lloyd、Andrew S. Thompson、Michael D. Threadgill

  DOI：10.1016/j.bmc.2013.06.031

  日期：2013.9

  Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of beta-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins. Treatment with ammonia at high temperature and reduction with tin(II) chloride gave eleven target 3-substituted 5-AIQs, which were all soluble in water (>1% w/ v) as their HCl salts. Most were more potent than 5-AIQ as inhibitors of PARP-1 and of PARP-2 in vitro, the most active being 5-amino-3-methylisoquinolin-1-one (PARP-1: IC50 = 0.23 mu M vs IC50 = 1.6 mu M for 5-AIQ). Some rationalisation of the SAR was achieved through molecular modelling. (C) 2013 Elsevier Ltd. All rights reserved.