Recent research and development of DYRK1A inhibitors

Zhao, Liyun; Xiong, Xuan; Liu, Li; Liang, Qi; Tong, Rongsheng; Feng, Xuanlin; Bai, Lan; Shi, Jianyou

doi:10.1016/j.cclet.2021.10.003

Cited by 8 publications

(2 citation statements)

References 128 publications

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“…Although some natural compounds, such as epigallocatechin-3-gallate (EGCG) [21], harmine [22], and leucettamine B [23], have been identified as potent inhibitors of DYRK1A or CLK1, significant research effort has been devoted to developing synthetic DYRK1A and/or CLK1 inhibitors based on relatively sophisticated heterocyclic scaffolds [7,19,[24][25][26][27][28]. A large majority of these kinase inhibitors are type I, that is, they bind to the active form of the kinase in the ATP pocket [29].…”

Section: Introductionmentioning

confidence: 99%

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

Ţînţaş

Peauger²,

Alix³

et al. 2022

Molecules

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The DYRK (Dual-specificity tyrosine phosphorylation-regulated kinase) family of protein kinases is involved in the pathogenesis of several neurodegenerative diseases. Among them, the DYRK1A protein kinase is thought to be implicated in Alzheimer’s disease (AD) and Down syndrome, and as such, has emerged as an appealing therapeutic target. DYRKs are a subset of the CMGC (CDK, MAPKK, GSK3 and CLK) group of kinases. Within this group of kinases, the CDC2-like kinases (CLKs), such as CLK1, are closely related to DYRKs and have also sparked great interest as potential therapeutic targets for AD. Based on inhibitors previously described in the literature (namely TG003 and INDY), we report in this work a new class of dihydroquinolines exhibiting inhibitory activities in the nanomolar range on hDYRK1A and hCLK1. Moreover, there is overwhelming evidence that oxidative stress plays an important role in AD. Pleasingly, the most potent dual kinase inhibitor 1p exhibited antioxidant and radical scavenging properties. Finally, drug-likeness and molecular docking studies of this new class of DYRK1A/CLK1 inhibitors are also discussed in this article.

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Section: Introductionmentioning

confidence: 99%

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

Ţînţaş

Peauger²,

Alix³

et al. 2022

Molecules

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“…Organophosphorus compounds with excellent biological activities and versatile reactivities, have been widely used in synthetic chemistry, [1][2][3] medicinal chemistry, [4][5][6][7] agriculture chemistry 8 and material chemistry. 9,10 Among them, C−3 phosphorylated 2Hindazoles have attracted considerable attentions due to the unique cytotoxic properties against cancer cells like A549 and HepG-2.…”

mentioning

confidence: 99%

Electrosynthesis of C−3 Phosphorylated 2H-Indazoles from Trialkyl Phosphites and 2H-Indazoles

Liu¹,

Yin²,

Wu³

et al. 2022

J. Electrochem. Soc.

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A facile and efficient direct electrochemical oxidation method for C−3 phosphorylation of 2H-indazoles with trialkyl phosphites as the phosphorylation reagents has been developed. Introducing electricity to the green and sustainable synthetic procedures allowed the reactions to be carried out under simple and mild conditions without any metal salts and additional oxidants. Electrochemical data showed that the cation radical species which were generated from the oxidation of 2H-indazoles were stabilized by 1,1,1,3,3,3-hexafluoro-2-propanol and could be captured by trialkyl phosphites effectively to form C−3 phosphorylated 2H-indazoles. In an undivided cell, a board range of functional groups on various substrates were well tolerated and the yield of the desired phosphorylated products was up to 84%. Moreover, a plausible mechanistic proposal involving radical pathway was established based on the results of cyclic voltammetry, in situ FTIR and control experiments.

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Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum

Lin

Huang

Zeng

et al. 2022

Chinese Chemical Letters

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Recent research and development of DYRK1A inhibitors

Cited by 8 publications

References 128 publications

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

Electrosynthesis of C−3 Phosphorylated 2H-Indazoles from Trialkyl Phosphites and 2H-Indazoles

Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum

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