3-chloro-2-[4-[4-(4-cyanophenyl)-3,6-dihydro-2H-pyridin-1-yl]butanoylamino]benzamide | 437998-61-3

• 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: 3-chloro-2-[4-[4-(4-cyanophenyl)-3,6-dihydro-2H-pyridin-1-yl]butanoylamino]benzamide
• CAS: 437998-61-3
• 化学式: C₂₃H₂₃ClN₄O₂
• 分子量: 422.914
• InChiKey: QLMOXEBCIQOEDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloro-2-[4-[4-(4-cyanophenyl)-3,6-dihydro-2H-pyridin-1-yl]butanoylamino]benzamide 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 15.0h， 生成 4-{1-[3-(8-Chloro-4-oxo-3,4-dihydroquinazolin-2-yl)propyl]-1,2,3,6-tetrahydropyridin-4-yl}benzonitrile
  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：

  2-氨基-3-氯苯甲酰胺 在 吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 3-chloro-2-[4-[4-(4-cyanophenyl)-3,6-dihydro-2H-pyridin-1-yl]butanoylamino]benzamide
  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

• Quinazolinone derivatives
  申请人：——

  公开号：US20040077667A1

  公开（公告）日：2004-04-22

  A quinazolinone derivatives having poly (adenosine 5′-diphaspho-ribose)polymerase (PARP) inhibotory activity represented by the formula (I), wherein R1 is optionally substituted cyclic amino groups or optionally substituted amino group, R2 is substituent, n means an integer from 0 to 4, and L is lower akkylene or lower alkenylene, or its prodrug, or their salts. 1

  一种具有聚(腺苷酸二磷酸核糖)聚合酶（PARP）抑制活性的喹唑啉酮衍生物，其化学式为（I），其中R1是可选取代的环氨基或可选取代的氨基基团，R2是取代基，n表示0至4的整数，L是低级别的取代基或低级别的烯基取代基，或其前药或盐。