methyl 3-fluoro-2-{(ethoxycarbonyl)[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butyl]amino}benzoate | 142375-03-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-fluoro-2-{(ethoxycarbonyl)[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butyl]amino}benzoate
• 英文别名: methyl 2-[ethoxycarbonyl-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]amino]-6-fluorobenzoate
• CAS: 142375-03-9
• 化学式: C₂₆H₃₁FN₂O₄
• 分子量: 454.542
• InChiKey: YPRSDYWRFLJFDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-fluoro-2-{(ethoxycarbonyl)[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butyl]amino}benzoate 在 氢氧化钾 、 氨 、 1-羟基苯并三唑一水物 、 N,N'-二异丙基碳二亚胺 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 5-Fluoro-1-[4-(4-phenyl-3,6-dihydropyridin-1(2H)-YL)butyl]quinazoline-2,4(1H,3H)-dione
  参考文献：
  名称：

  Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling

  摘要：

  We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinant PARP-1 and PARP-2, the quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2, and the quinazolidinone derivatives did not have selectivity for PARP-1/2. Structure-based drug design analysis via a combination of X-ray structural study utilizing the complexes of inhibitors and human PARP-1 catalytic domain, and homology modeling using murine PARP-2 suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.061
• 作为产物：
  描述：

  Methyl 2-[4-chlorobutyl(ethoxycarbonyl)amino]-6-fluorobenzoate 、 1,2,3,6-四氢-4-苯基吡啶盐酸盐 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以89%的产率得到methyl 3-fluoro-2-{(ethoxycarbonyl)[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butyl]amino}benzoate
  参考文献：
  名称：

  Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling

  摘要：

  We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinant PARP-1 and PARP-2, the quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2, and the quinazolidinone derivatives did not have selectivity for PARP-1/2. Structure-based drug design analysis via a combination of X-ray structural study utilizing the complexes of inhibitors and human PARP-1 catalytic domain, and homology modeling using murine PARP-2 suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.09.061

文献信息

• Quinazoline derivatives and their preparation
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0481342A1

  公开（公告）日：1992-04-22

  A compound of the formula : in which R1 and R2 are each hydrogen, halogen, nitro, amino, protected amino, hydroxyamino, lower alkoxy, lower alkyl, hydroxy, sulfamoyl, carboxy, protected carboxy, carbamoyl, mercapto, lower alkylthio or imidazolyl, R3 is aryl which may have suitable substituent(s), A is lower alkylene, and the formula: is N-containing heterocylcic group, or pharmaceutically acceptable salts thereof, processes for their preparation and pharmaceutical compositions comprising them in admixture with a pharmaceutically acceptable carrier or excipient.

  式中的化合物： 其中 R1 和 R2 分别为氢、卤素、硝基、 氨基、受保护氨基、羟基氨基、低级烷氧基、低级烷基、羟基、氨基磺酰基、羧基、 受保护羧基、氨基甲酰基、巯基、低级烷硫基或咪唑基、 R3 是芳基，可带有合适的取代基、 A 是低级亚烷基，式中 是 含 N 的杂环基团或其药学上可接受的盐、其制备方法以及由它们与药学上可接受的载体或赋形剂混合而成的药物组合物。
• US5304560A
  申请人：——

  公开号：US5304560A

  公开（公告）日：1994-04-19