3-(3,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine | 1492681-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(3,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 5-(2,5-dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine
• CAS: 1492681-67-0
• 化学式: C₂₃H₂₂N₂O₄
• 分子量: 390.439
• InChiKey: PGGSIXVEVLPEAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以41%的产率得到3-(3,4-dihydroxyphenyl)-5-(2,5-dihydroxyphenyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Development of DANDYs, New 3,5-Diaryl-7-azaindoles Demonstrating Potent DYRK1A Kinase Inhibitory Activity

  摘要：

  A series of 3,5-diaryl-1H-pyrrolo[2,3-b]pyridines were synthesized and evaluated for inhibition of DYRKIA kinase in vitro. Derivatives having hydroxy groups on the aryl moieties (2c, 2j-l) demonstrated high inhibitory potencies with K(i)s in the low nanomolar range. Their methoxy analogues were up to 100 times less active. Docking studies at the ATP binding site suggested that these compounds bind tightly to this site via a network of multiple H-bonds with the peptide backbone. None of the active compounds were cytotoxic to KB cells at 10(-6) M. Kinase profiling revealed that compound 2j showed 2-fold selectivity for DYRK1A with respect to DYRK2 and DYRK3.

  DOI：

  10.1021/jm401049v
• 作为产物：
  描述：

  3-(3,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以29%的产率得到3-(3,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Development of DANDYs, New 3,5-Diaryl-7-azaindoles Demonstrating Potent DYRK1A Kinase Inhibitory Activity

  摘要：

  A series of 3,5-diaryl-1H-pyrrolo[2,3-b]pyridines were synthesized and evaluated for inhibition of DYRKIA kinase in vitro. Derivatives having hydroxy groups on the aryl moieties (2c, 2j-l) demonstrated high inhibitory potencies with K(i)s in the low nanomolar range. Their methoxy analogues were up to 100 times less active. Docking studies at the ATP binding site suggested that these compounds bind tightly to this site via a network of multiple H-bonds with the peptide backbone. None of the active compounds were cytotoxic to KB cells at 10(-6) M. Kinase profiling revealed that compound 2j showed 2-fold selectivity for DYRK1A with respect to DYRK2 and DYRK3.

  DOI：

  10.1021/jm401049v

文献信息

• 3,5-Diarylazaindoles as DYRK1A Protein Inhibitors for the Treatment of Cognitive Deficiencies Associated with Down's Syndrome and with Alzheimer's Disease
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：US20150307492A1

  公开（公告）日：2015-10-29

  The present invention relates to a compound of formula (I′) or a pharmaceutically acceptable salt, solvate or hydrate thereof, in which: X 3 is F, OH or SH, Y 3 is F, OH or SH, X 1 , X 2 , X 4 , X 5 , Y 1 , Y 2 , Y 4 and Y 5 are, independently of one another, H, F, Cl, Br, OH or SH, and 1 to 2 groups among the X 1 , X 2 , X 4 and X 5 radicals are other than H and/or 1 to 2 groups among the Y 1 , Y 2 , Y 4 and Y 5 radicals are other than H. The present invention also relates to a compound of formula (I′) for use as a medicament, in particular in the prevention and/or treatment of cognitive disorders associated with a dysfunction of the Dyrk1A protein.

  本发明涉及一种具有以下结构的化合物（I′）或其药学上可接受的盐、溶剂或水合物，其中：X3为F、OH或SH，Y3为F、OH或SH，X1、X2、X4、X5、Y1、Y2、Y4和Y5分别独立地为H、F、Cl、Br、OH或SH，且在X1、X2、X4和X5基团中的1到2个基团不是H，和/或在Y1、Y2、Y4和Y5基团中的1到2个基团不是H。本发明还涉及一种具有结构式（I′）的化合物，用作药物，特别是用于预防和/或治疗与Dyrk1A蛋白功能障碍相关的认知障碍。
• US9447093B2
  申请人：——

  公开号：US9447093B2

  公开（公告）日：2016-09-20
• Development of DANDYs, New 3,5-Diaryl-7-azaindoles Demonstrating Potent DYRK1A Kinase Inhibitory Activity
  作者：Stéphanie Gourdain、Julien Dairou、Clément Denhez、Linh Chi Bui、Fernando Rodrigues-Lima、Nathalie Janel、Jean M. Delabar、Kevin Cariou、Robert H. Dodd

  DOI：10.1021/jm401049v

  日期：2013.12.12

  A series of 3,5-diaryl-1H-pyrrolo[2,3-b]pyridines were synthesized and evaluated for inhibition of DYRKIA kinase in vitro. Derivatives having hydroxy groups on the aryl moieties (2c, 2j-l) demonstrated high inhibitory potencies with K(i)s in the low nanomolar range. Their methoxy analogues were up to 100 times less active. Docking studies at the ATP binding site suggested that these compounds bind tightly to this site via a network of multiple H-bonds with the peptide backbone. None of the active compounds were cytotoxic to KB cells at 10(-6) M. Kinase profiling revealed that compound 2j showed 2-fold selectivity for DYRK1A with respect to DYRK2 and DYRK3.