3-(pyridin-4-yl)-1H-pyrrolo[2,3-c]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-(pyridin-4-yl)-1H-pyrrolo[2,3-c]pyridine
• 英文别名: 3-pyridin-4-yl-1H-pyrrolo[2,3-c]pyridine
• 化学式: C₁₂H₉N₃
• 分子量: 195.224
• InChiKey: KURWIPZCULOEEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-羟丙基)吗啉 、 3-(pyridin-4-yl)-1H-pyrrolo[2,3-c]pyridine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 4-[3-(3-Pyridin-4-ylpyrrolo[2,3-c]pyridin-1-yl)propyl]morpholine
  参考文献：
  名称：

  Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus

  摘要：

  A structure-activity relationship has been developed around the meridianin scaffold for inhibition of Dyrk1a. The compounds have been focussed on the inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT in the nucleus. NFAT is responsible for up-regulation of genes responsible for the induction of a slow, oxidative skeletal muscle phenotype, which may be an effective treatment for diseases where exercise capacity is compromised. The SAR showed that while strong Dyrk1a binding was possible with the meridianin scaffold the compounds have no effect on NFAT localisation, however, by moving from the indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT residence time in the nucleus were obtained - properties not observed with the reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo muscle fiber assay. The increased biological activity is thought to arise from the added interaction between the azaindole nitrogen and the lysine residue in the back pocket. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.037
• 作为产物：
  描述：

  1-benzenesulfonyl-3-iodo-1H-pyrrolo[2,3-c]pyridine 在 四(三苯基膦)钯 、 sodium methylate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 1.75h， 生成 3-(pyridin-4-yl)-1H-pyrrolo[2,3-c]pyridine
  参考文献：
  名称：

  Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus

  摘要：

  A structure-activity relationship has been developed around the meridianin scaffold for inhibition of Dyrk1a. The compounds have been focussed on the inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT in the nucleus. NFAT is responsible for up-regulation of genes responsible for the induction of a slow, oxidative skeletal muscle phenotype, which may be an effective treatment for diseases where exercise capacity is compromised. The SAR showed that while strong Dyrk1a binding was possible with the meridianin scaffold the compounds have no effect on NFAT localisation, however, by moving from the indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT residence time in the nucleus were obtained - properties not observed with the reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo muscle fiber assay. The increased biological activity is thought to arise from the added interaction between the azaindole nitrogen and the lysine residue in the back pocket. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.037

文献信息

• Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133
  作者：Yahu A. Liu、Qihui Jin、Yefen Zou、Qiang Ding、Shanshan Yan、Zhicheng Wang、Xueshi Hao、Bao Nguyen、Xiaoyue Zhang、Jianfeng Pan、Tingting Mo、Kate Jacobsen、Thanh Lam、Tom Y.-H. Wu、H. Michael Petrassi、Badry Bursulaya、Michael DiDonato、W. Perry Gordon、Bo Liu、Janine Baaten、Robert Hill、Vân Nguyen-Tran、Minhua Qiu、You-Qing Zhang、Anwesh Kamireddy、Sheryll Espinola、Lisa Deaton、Sukwon Ha、George Harb、Yong Jia、Jing Li、Weijun Shen、Andrew M. Schumacher、Karyn Colman、Richard Glynne、Shifeng Pan、Peter McNamara、Bryan Laffitte、Shelly Meeusen、Valentina Molteni、Jon Loren

  DOI：10.1021/acs.jmedchem.9b01624

  日期：2020.3.26

  Autoimmune deficiency and destruction in either beta-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting beta-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit. In vitro, GNF2133 is able to proliferate both rodent and human beta-cells. In vivo, GNF2133 demonstrated significant dose-dependent glucose disposal capacity and insulin secretion in response to glucose-potentiated arginine-induced insulin secretion (GPAIS) challenge in rat insulin promoter and diphtheria toxin A (RIP-DTA) mice. The work described here provides new avenues to disease altering therapeutic interventions in the treatment of type 1 diabetes (T1D).
• [EN] COMPOUNDS FOR USE IN TREATING NEUROLOGICAL DISORDERS<br/>[FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：[en]PROTHENA BIOSCIENCES LIMITED

  公开号：WO2023107722A1

  公开（公告）日：2023-06-15

  This disclosure provides compounds of formula (I) and pharmaceutically acceptable salts thereof, that inhibit Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). These chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) DYRK1A activation contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., a neurological disorder) in a subject (e.g., a human). This disclosure also provides compositions containing the same as well as methods of using and making the same.
• Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus
  作者：Simon J. Shaw、Dane A. Goff、Nan Lin、Rajinder Singh、Wei Li、John McLaughlin、Kristen A. Baltgalvis、Donald G. Payan、Todd M. Kinsella

  DOI：10.1016/j.bmcl.2017.03.037

  日期：2017.6

  A structure-activity relationship has been developed around the meridianin scaffold for inhibition of Dyrk1a. The compounds have been focussed on the inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT in the nucleus. NFAT is responsible for up-regulation of genes responsible for the induction of a slow, oxidative skeletal muscle phenotype, which may be an effective treatment for diseases where exercise capacity is compromised. The SAR showed that while strong Dyrk1a binding was possible with the meridianin scaffold the compounds have no effect on NFAT localisation, however, by moving from the indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT residence time in the nucleus were obtained - properties not observed with the reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo muscle fiber assay. The increased biological activity is thought to arise from the added interaction between the azaindole nitrogen and the lysine residue in the back pocket. (C) 2017 Elsevier Ltd. All rights reserved.