(E)-3-((dipropylamino)methylene)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one

• 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: (E)-3-((dipropylamino)methylene)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one
• 英文别名: (3E)-3-[(dipropylamino)methylidene]-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one
• 化学式: C₁₈H₂₃N₃O
• 分子量: 297.4
• InChiKey: IZJTZPDQRHWYTC-BUHFOSPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  35.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-(2-benzamido)-4-chlorobutanamide 在 potassium tert-butylate 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 (E)-3-((dipropylamino)methylene)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one
  参考文献：
  名称：

  Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex

  摘要：

  Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a K-D of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.

  DOI：

  10.1021/acs.jmedchem.5b01997

文献信息

• [EN] SMARCA DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE SMARCA ET LEURS UTILISATIONS
  申请人：KYMERA THERAPEUTICS INC

  公开号：WO2020251971A1

  公开（公告）日：2020-12-17

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and/or PB1 proteins.

  本发明提供化合物、其药学上可接受的组合物，以及利用这些化合物调控一个或多个SWI/SNF相关基质相关肌动蛋白依赖的染色质亚家族A（SMARCA）和/或聚溴-1（PB-1）蛋白通过化合物的泛素化和/或降解的方法。这些化合物是双功能分子，将结合到cereblon的部分与结合到SMARCA和/或PB1蛋白的配体连接在一起。
• Identification and Development of 2,3-Dihydropyrrolo[1,2-<i>a</i>]quinazolin-5(1<i>H</i>)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex
  作者：Charlotte L. Sutherell、Cynthia Tallant、Octovia P. Monteiro、Clarence Yapp、Julian E. Fuchs、Oleg Fedorov、Paulina Siejka、Suzanne Müller、Stefan Knapp、James D. Brenton、Paul E. Brennan、Steven V. Ley

  DOI：10.1021/acs.jmedchem.5b01997

  日期：2016.5.26

  Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a K-D of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4.