scholarly journals Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors

2021 ◽  
Author(s):  
Julia Stille ◽  
Jevgenijs Tjutrins ◽  
Guanyu Wang ◽  
Felipe A. Venegas ◽  
Christopher Hennecker ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Antiviral Drugs ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Promising Target ◽  
Starting Point ◽  
Covalent Inhibitors ◽  
Screening Platform ◽  
And Function ◽  
Synthesis And Biological Evaluation

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro> has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in design and synthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

scholarly journals Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors

2020 ◽  
Author(s):  
Julia Stille ◽  
Jevgenijs Tjutrins ◽  
Guanyu Wang ◽  
Felipe A. Venegas ◽  
Christopher Hennecker ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Antiviral Drugs ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Promising Target ◽  
Starting Point ◽  
Covalent Inhibitors ◽  
Screening Platform ◽  
And Function ◽  
Synthesis And Biological Evaluation

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in design and synthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

scholarly journals Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors

2021 ◽  
Author(s):  
Julia Stille ◽  
Jevgenijs Tjutrins ◽  
Guanyu Wang ◽  
Felipe A. Venegas ◽  
Christopher Hennecker ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Antiviral Drugs ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Promising Target ◽  
Starting Point ◽  
Covalent Inhibitors ◽  
Screening Platform ◽  
And Function ◽  
Synthesis And Biological Evaluation

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL<sup>pro</sup> has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL<sup>pro</sup> non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL<sup>pro</sup>. We report herein our efforts in design and synthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

scholarly journals Design, Synthesis and Biological Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors

2020 ◽  
Author(s):  
Julia Stille ◽  
Jevgenijs Tjutrins ◽  
Guanyu Wang ◽  
Felipe A. Venegas ◽  
Christopher Hennecker ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Antiviral Drugs ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Promising Target ◽  
Starting Point ◽  
Covalent Inhibitors ◽  
Screening Platform ◽  
And Function ◽  
Synthesis And Biological Evaluation

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CLpro has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CLpro non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CLpro. We report herein our efforts in design and synthesis which led to submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

scholarly journals Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors

MedChemComm ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 149-159 ◽  
Author(s):  
Gaochan Wu ◽  
Yun Gao ◽  
Dongwei Kang ◽  
Boshi Huang ◽  
Zhipeng Huo ◽  
...  
Keyword(s):  
Cholinesterase Inhibitors ◽  
Biological Evaluation ◽  
Dipolar Cycloaddition ◽  
Design Synthesis ◽  
Triazole Derivatives ◽  
Design And Synthesis ◽  
Cuaac Reaction ◽  
Synthesis And Biological Evaluation

We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3-triazole derivatives via a Cu(i)-catalyzed alkyne–azide 1,3-dipolar cycloaddition (CuAAC) reaction.

scholarly journals Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against Pseudomonas aeruginosa Resistance

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3103
Author(s):  
Shekh Sabir ◽  
Sujatha Subramoni ◽  
Theerthankar Das ◽  
David StC. Black ◽  
Scott A. Rice ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Adenosine Monophosphate ◽  
Biological Evaluation ◽  
Bacterial Biofilms ◽  
Design Synthesis ◽  
Signaling Systems ◽  
Design And Synthesis ◽  
Bacterial Aggregation ◽  
Synthesis And Biological Evaluation

The Pseudomonas quinolone system (PQS) is one of the three major interconnected quorum sensing signaling systems in Pseudomonas aeruginosa. The virulence factors PQS and HHQ activate the transcription regulator PqsR (MvfR), which controls several activities in bacteria, including biofilm formation and upregulation of PQS biosynthesis. The enzyme anthraniloyl-CoA synthetase (PqsA) catalyzes the first and critical step in the biosynthesis of quinolones; therefore, it is an attractive target for the development of anti-virulence therapeutics against Pseudomonas resistance. Herein, we report the design and synthesis of novel triazole nucleoside-based anthraniloyl- adenosine monophosphate (AMP) mimics. These analogues had a major impact on the morphology of bacterial biofilms and caused significant reduction in bacterial aggregation and population density. However, the compounds showed only limited inhibition of PQS and did not exhibit any effect on pyocyanin production.

Design, synthesis and biological evaluation of FLT3 covalent inhibitors with a resorcylic acid core

2014 ◽  
Vol 22 (23) ◽  
pp. 6625-6637 ◽  
Author(s):  
Jin Xu ◽  
Esther H.Q. Ong ◽  
Jeffrey Hill ◽  
Anqi Chen ◽  
Christina L.L. Chai
Keyword(s):  
Biological Evaluation ◽  
Design Synthesis ◽  
Covalent Inhibitors ◽  
Synthesis And Biological Evaluation

scholarly journals Design, Synthesis and Biological Evaluation of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-Substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

2016 ◽  
Author(s):  
Zhen Zhang ◽  
Dongmei Zhao ◽  
Yang Dai ◽  
Maosheng Cheng ◽  
Meiyu Geng ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Biological Evaluation ◽  
Fibroblast Growth ◽  
Design Synthesis ◽  
Promising Target ◽  
Cancer Types ◽  
Synthesis And Biological Evaluation

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Sign in / Sign up

Export Citation Format

Share Document