2,9-dicyanopaullone | 1019995-58-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2,9-dicyanopaullone
• 英文别名: 6-oxo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepine-2,9-dicarbonitrile
• CAS: 1019995-58-4
• 化学式: C₁₈H₁₀N₄O
• 分子量: 298.304
• InChiKey: FSCLZTCYWFNGON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,5-dioxo-2,3,4,5-tetrahydro-1H-1-benzazepine-7-carbonitrile 、 4-氰基苯肼盐酸盐 在 sodium acetate 、 溶剂黄146 、 硫酸 作用下， 反应 4.0h， 生成 2,9-dicyanopaullone
  参考文献：
  名称：

  9-Cyano-1-azapaullone (Cazpaullone), a Glycogen Synthase Kinase-3 (GSK-3) Inhibitor Activating Pancreatic β Cell Protection and Replication

  摘要：

  Recently, the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) emerged as a regulator of pancreatic beta cell growth and survival. On the basis of the previous observation that GSK-3 inhibitors like 1-azakenpaullone promote beta cell protection and replication, paullone derivatives were synthesized including 1-aza-, 2-aza-, and 12-oxapaullone scaffolds. In enzymatic assays distinct 1-azapaullones were found to exhibit selective GSK-3 inhibitory activity. Within the series of 1-azapaullones, three derivatives stimulated INS-1E beta cell replication and protected INS-1E cells against glucolipotoxicity induced cell death. Cazpaullone (9-cyano-1-azapaullone), the most active compound in the protection assays, also stimulated the replication of primary beta cells in isolated rat islets. Furthermore, cazpaullone showed a pronounced transient stimulation of the mRNA expression of the beta cell transcription factor Pax4, an important regulator of beta cell development and growth. These features distinguish cazpaullone as a unique starting point for the development of beta cell regenerative agents which might be useful in the treatment of diabetes.

  DOI：

  10.1021/jm701582f

文献信息

• METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTIONAL MODULATORS
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20160030445A1

  公开（公告）日：2016-02-04

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27 Kip1 , or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Methods and Compositions of P27KIP1 Transcriptional Modulators
  申请人：St. Jude Children's Research Hospital

  公开号：US20170189477A1

  公开（公告）日：2017-07-06

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof and agents that inhibit the expression of p27 Kip1 , or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• US9572815B2
  申请人：——

  公开号：US9572815B2

  公开（公告）日：2017-02-21
• [EN] METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTION MODULATORS<br/>[FR] PROCÉDÉS ET COMPOSITIONS DE MODULATEURS DE LA TRANSCRIPTION DE P27KIP1
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2014145205A2

  公开（公告）日：2014-09-18

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27Kipl, or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• 9-Cyano-1-azapaullone (Cazpaullone), a Glycogen Synthase Kinase-3 (GSK-3) Inhibitor Activating Pancreatic β Cell Protection and Replication
  作者：Hendrik Stukenbrock、Rainer Mussmann、Marcus Geese、Yoan Ferandin、Olivier Lozach、Thomas Lemcke、Simone Kegel、Alexander Lomow、Ulrike Burk、Cord Dohrmann、Laurent Meijer、Matthias Austen、Conrad Kunick

  DOI：10.1021/jm701582f

  日期：2008.4.1

  Recently, the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) emerged as a regulator of pancreatic beta cell growth and survival. On the basis of the previous observation that GSK-3 inhibitors like 1-azakenpaullone promote beta cell protection and replication, paullone derivatives were synthesized including 1-aza-, 2-aza-, and 12-oxapaullone scaffolds. In enzymatic assays distinct 1-azapaullones were found to exhibit selective GSK-3 inhibitory activity. Within the series of 1-azapaullones, three derivatives stimulated INS-1E beta cell replication and protected INS-1E cells against glucolipotoxicity induced cell death. Cazpaullone (9-cyano-1-azapaullone), the most active compound in the protection assays, also stimulated the replication of primary beta cells in isolated rat islets. Furthermore, cazpaullone showed a pronounced transient stimulation of the mRNA expression of the beta cell transcription factor Pax4, an important regulator of beta cell development and growth. These features distinguish cazpaullone as a unique starting point for the development of beta cell regenerative agents which might be useful in the treatment of diabetes.