1-(3-aminobenzyl)quinazoline-2,4(1H,3H)-dione | 1401684-06-7

• 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: 1-(3-aminobenzyl)quinazoline-2,4(1H,3H)-dione
• 英文别名: 1-[(3-Aminophenyl)methyl]quinazoline-2,4-dione；1-[(3-aminophenyl)methyl]quinazoline-2,4-dione
• CAS: 1401684-06-7
• 化学式: C₁₅H₁₃N₃O₂
• 分子量: 267.287
• InChiKey: XYQNTTHXWAYWFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-aminobenzyl)quinazoline-2,4(1H,3H)-dione 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 (R)-N-(3-((2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)phenyl)pyrrolidine-2-carboxamide 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Discovery of 1-substituted benzyl-quinazoline-2,4(1H,3H)-dione derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors

  摘要：

  Poly(ADP-ribose)polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. In this work, a novel series of 1-benzyl-quinazoline-2,4(1H,3H)-dione derivatives were designed and synthesized as human PARP-1 inhibitors, structure-activity relationships were conducted and led to a number of potent PARP-1 inhibitors having IC50 values of single or double digit nanomolar level. Compound 7j was a potent PARP-1 and PARP-2 inhibitor and it could selectively kill the breast cancer cells MX-1 and MDA-MB-468 with mutated BRCA1/2 and PTEN, respectively, in comparison with homologous recombination proficient cell types such as breast cancer cells MDA-MB-231. In addition, compound 7j displayed the strongest potentiation effect on temozolomide in MX-1 cells (PF50 = 3.77) in this series of PARP-1 inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.071
• 作为产物：
  描述：

  1-(3-nitrobenzyl)quinazoline-2,4(1H,3H)-dione 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 以98.2%的产率得到1-(3-aminobenzyl)quinazoline-2,4(1H,3H)-dione
  参考文献：
  名称：

  Discovery of 1-substituted benzyl-quinazoline-2,4(1H,3H)-dione derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors

  摘要：

  Poly(ADP-ribose)polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. In this work, a novel series of 1-benzyl-quinazoline-2,4(1H,3H)-dione derivatives were designed and synthesized as human PARP-1 inhibitors, structure-activity relationships were conducted and led to a number of potent PARP-1 inhibitors having IC50 values of single or double digit nanomolar level. Compound 7j was a potent PARP-1 and PARP-2 inhibitor and it could selectively kill the breast cancer cells MX-1 and MDA-MB-468 with mutated BRCA1/2 and PTEN, respectively, in comparison with homologous recombination proficient cell types such as breast cancer cells MDA-MB-231. In addition, compound 7j displayed the strongest potentiation effect on temozolomide in MX-1 cells (PF50 = 3.77) in this series of PARP-1 inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.071

文献信息

• 1-(Arylmethyl)quinazoline-2,4(1H,3H)-diones as PARP Inhibitors and the Use Thereof
  申请人：Cai Sui Xiong

  公开号：US20140023642A1

  公开（公告）日：2014-01-23

  Disclosed are 1-(arylmethyl)quinazoline-2,4(1H,3H)-diones thereof, represented by the Formula (I) wherein Ar, R 1 -R 6 are defined herein. Compounds having Formula (I) are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity.

  公开的是其1-(芳基甲基)喹唑啉-2,4(1H,3H)-二酮，由式(I)所代表，其中Ar，R1-R6在此定义。具有式(I)的化合物为PARP抑制剂。因此，本发明的化合物可用于治疗对PARP活性抑制有响应的临床病况。
• 1-(Arylmethyl)quinazoline-2,4(1H,3H)-Diones as PARP Inhibitors and the Use Thereof
  申请人：Impact Therapeutics, Inc.

  公开号：US20160237070A1

  公开（公告）日：2016-08-18

  Disclosed are 1-(arylmethyl)quinazoline-2,4(1H,3H)-diones represented by the Formula (I): wherein Ar, R 1 -R 6 are defined herein. Compounds having Formula (I) are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity.

  本发明涉及一种由式（I）表示的1-(芳基甲基)喹唑啉-2,4(1H,3H)-二酮，其中Ar，R1-R6如本文所定义。具有式（I）的化合物是PARP抑制剂。因此，本发明的化合物可以用于治疗对PARP活性抑制有反应的临床病症。
• 1-(arylmethyl)quinazoline-2,4(1H,3H)-diones as PARP inhibitors and the use thereof
  申请人：IMPACT Therapeutics, Inc.

  公开号：US10316027B2

  公开（公告）日：2019-06-11

  Disclosed are 1-(arylmethyl)quinazoline-2,4(1H,3H)-diones represented by the Formula (I): wherein Ar, R1-R6, are defined herein. Compounds having Formula (I) are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity.

  本发明公开了由式 (I) 代表的 1-(芳基甲基)喹唑啉-2,4(1H,3H)-二酮： 其中 Ar、R1-R6 在本文中定义。具有式（I）的化合物是 PARP 抑制剂。因此，本发明的化合物可用于治疗对抑制 PARP 活性有反应的临床病症。
• 1-((3-((1-Piperazinyl)carbonyl)phenyl)methyl)-2,4(1H,3H)-quinazolinedione derivatives as PARP inhibitors for treating cancer
  申请人：Impact Therapeutics, Inc.

  公开号：EP2709990B1

  公开（公告）日：2019-06-12
• US9290460B2
  申请人：——

  公开号：US9290460B2

  公开（公告）日：2016-03-22