5-Fluoro-1-[4-(4-phenyl-3,6-dihydropyridin-1(2H)-YL)butyl]quinazoline-2,4(1H,3H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-Fluoro-1-[4-(4-phenyl-3,6-dihydropyridin-1(2H)-YL)butyl]quinazoline-2,4(1H,3H)-dione
• 英文别名: 5-fluoro-1-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]quinazoline-2,4-dione
• 化学式: C₂₃H₂₄FN₃O₂
• 分子量: 393.461
• InChiKey: PNPFDRCIGCUCMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,2,3,6-四氢-4-苯基吡啶盐酸盐 在 氢氧化钾 、 氨 、 potassium carbonate 、 1-羟基苯并三唑一水物 、 sodium iodide 、 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 20.0h， 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

文献信息

• THERAPEUTIC KINASE MODULATORS
  申请人：PIERRE Fabrice

  公开号：US20090093465A1

  公开（公告）日：2009-04-09

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, and modulating protein kinase activity. Molecules of the invention can modulate casein kinase (CK) activity. The invention also relates in part to methods for using such molecules.

  该发明涉及部分具有特定生物活性的分子，包括但不限于抑制细胞增殖和调节蛋白激酶活性。该发明的分子可以调节酪蛋白激酶（CK）活性。该发明还涉及使用这些分子的方法。
• SERINE-THREONINE PROTEIN KINASE AND PARP MODULATORS
  申请人：CHUA Peter

  公开号：US20090264423A2

  公开（公告）日：2009-10-22

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

  本发明涉及具有某些生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。本发明的分子可以调节酪蛋白激酶（CK）活性和/或聚(ADP-核糖)聚合酶（PARP）活性。本发明还涉及使用这些分子的方法。
• FUSED TRICYCLIC COMPOUNDS AS SERINE-THREONINE PROTEIN KINASE AND PARP MODULATORS
  申请人：CHUA Peter C.

  公开号：US20110263581A1

  公开（公告）日：2011-10-27

  The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

  本发明部分涉及具有某些生物活性的分子，包括但不限于抑制细胞增殖、调节蛋白激酶活性和调节聚合酶活性。本发明的分子可以调节酪氨酸激酶（CK）活性和/或聚(ADP核糖)聚合酶（PARP）活性。本发明部分还涉及使用这些分子的方法。
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.