2-{[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butanoyl]amino}benzamide | 437998-41-9

• 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: 2-{[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butanoyl]amino}benzamide
• 英文别名: 2-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butanoylamino]benzamide
• CAS: 437998-41-9
• 化学式: C₂₂H₂₅N₃O₂
• 分子量: 363.459
• InChiKey: FRQUZVALJWDLHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  2-{[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butanoyl]amino}benzamide 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以72.9%的产率得到2-{3-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]propyl}-4(3H)-quinazolinone
  参考文献：
  名称：

  合理的方法来发现聚（ADP-核糖）聚合酶的口服活性和脑可穿透的喹唑啉酮抑制剂。

  摘要：

  已发现一类新型的喹唑啉酮衍生物作为有效的聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。成功的关键是应用合理的发现策略，包括基于结构的设计，组合化学和经典SAR，以提高药效和生物利用度。新抑制剂被显示与NAD +的烟酰胺-核糖结合位点（NI位点）和腺苷-核糖结合位点（AD位点）结合。

  DOI：

  10.1021/jm0499256
• 作为产物：
  描述：

  2-氨基苯甲酰胺 在 吡啶 、 三乙胺 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 2-{[4-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)butanoyl]amino}benzamide
  参考文献：
  名称：

  合理的方法来发现聚（ADP-核糖）聚合酶的口服活性和脑可穿透的喹唑啉酮抑制剂。

  摘要：

  已发现一类新型的喹唑啉酮衍生物作为有效的聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。成功的关键是应用合理的发现策略，包括基于结构的设计，组合化学和经典SAR，以提高药效和生物利用度。新抑制剂被显示与NAD +的烟酰胺-核糖结合位点（NI位点）和腺苷-核糖结合位点（AD位点）结合。

  DOI：

  10.1021/jm0499256

文献信息

• Rational Approaches to Discovery of Orally Active and Brain-Penetrable Quinazolinone Inhibitors of Poly(ADP-ribose)polymerase
  作者：Kouji Hattori、Yoshiyuki Kido、Hirofumi Yamamoto、Junya Ishida、Kazunori Kamijo、Kenji Murano、Mitsuru Ohkubo、Takayoshi Kinoshita、Akinori Iwashita、Kayoko Mihara、Syunji Yamazaki、Nobuya Matsuoka、Yoshinori Teramura、Hiroshi Miyake

  DOI：10.1021/jm0499256

  日期：2004.8.1

  A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and

  已发现一类新型的喹唑啉酮衍生物作为有效的聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。成功的关键是应用合理的发现策略，包括基于结构的设计，组合化学和经典SAR，以提高药效和生物利用度。新抑制剂被显示与NAD +的烟酰胺-核糖结合位点（NI位点）和腺苷-核糖结合位点（AD位点）结合。
• 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。
• Quinazolinone derivative
  申请人：Ishida Junya

  公开号：US20050043333A1

  公开（公告）日：2005-02-24

  A quinazolinone derivatives having poly (adenosine 5′-diphospho-ribose) polymerase (PARP) inhibitory activity represented by the formula (I): wherein R 1 is substituted cyclic amino groups or optionally substituted amino group, R 2 is substituent, n means an integer of 0 to 4, and L 1 is (1) cyclo (lower) alkylene, (2) cyclo (lower) alkenylene, (3) diradical of saturated- or unsaturated monocyclic group with one or more nitrogen atom(s), which is obtained after removal of one hydrogen atom from said monocyclic group, or (4) —N(R 3 )—L 2 — (wherein R 3 is hydrogen or lower alkyl, and L 2 is lower alkylene or lower alkenylene), or its prodrug, or a salt thereof.

  具有聚腺苷酸二磷酸核糖酶（PARP）抑制活性的喹唑啉酮衍生物，其化学式表示为（I）：其中R1是取代的环氨基或可选取代的氨基基团，R2是取代基，n是0到4的整数，L1是（1）环（低）烷基，（2）环（低）烯基，（3）饱和或不饱和单环基的二自由基，其中该单环基上的一个或多个氢原子被去除后获得，或（4）—N（R3）—L2—（其中R3是氢或低烷基，L2是低烷基或低烯基烷基），或其前药，或其盐。
• Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling
  作者：Junya Ishida、Hirofumi Yamamoto、Yoshiyuki Kido、Kazunori Kamijo、Kenji Murano、Hiroshi Miyake、Mitsuru Ohkubo、Takayoshi Kinoshita、Masaichi Warizaya、Akinori Iwashita、Kayoko Mihara、Nobuya Matsuoka、Kouji Hattori

  DOI：10.1016/j.bmc.2005.09.061

  日期：2006.3

  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.