Highly regioselective and stereoselective synthesis of C-Aryl glycosides via Nickel-catalyzed ortho-C-H glycosylation of 8-aminoquinoline benzamides

Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost-effective approach in early drug discovery. If structures of active compounds are available, rapid 2D similarity search can be performed on multimillion compounds’ databases. This approach can be combined with physico-chemical parameter and diversity filtering, bioisosteric replacements, and fragment-based approaches for performing a first round biological screening. Our objectives were to investigate the combination of 2D similarity search with various 3D ligand and structure-based methods for hit expansion and validation, in order to increase the hit rate and novelty. In the present account, six case studies are described and the efficiency of mixing is evaluated. While sequentially combined 2D/3D similarity approach increases the hit rate significantly, sequential combination of 2D similarity with pharmacophore model or 3D docking enriched the resulting focused library with novel chemotypes. Parallel integrated approaches allowed the comparison of the various 2D and 3D methods and revealed that 2D similarity-based and 3D ligand and structure-based techniques are often complementary, and their combinations represent a powerful synergy. Finally, the lessons we learnt including the advantages and pitfalls of the described approaches are discussed.

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A Metal-free and β-Stereoselective Synthesis of 2-Deoxy-C-aryl Glycosides: Synthesis of 5-aza analogues of Aquayamycin

Synlett ◽

10.1055/a-1670-2290 ◽

2021 ◽

Author(s):

Yuling Mei ◽

nan jiang ◽

Yu Yang ◽

Wan Zhang ◽

Saifeng Qiu ◽

...

Keyword(s):

Stereoselective Synthesis ◽

Metal Free ◽

Wide Range ◽

One Step ◽

Aryl Glycosides ◽

Aryl Glycoside

A convenient protocol for β-stereoselective synthesis of 2-deoxy-C-aryl glycosides has been developed. This reaction takes place in one step by using I2/Et3SiH to activate glycosyl acetate to generate glycosyl iodide intermediate in situ, which was captured by naphthol followed by Fries-like O- → C-glycoside rearrangement to selectively afford β-C-aryl glycoside. The approach is applicable to a wide range of naphthol modules, and its utility was demonstrated in the synthesis of 5-aza analogues of Aquayamycin.

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Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

Molecules ◽

10.3390/molecules25020401 ◽

2020 ◽

Vol 25 (2) ◽

pp. 401 ◽

Cited By ~ 4

Author(s):

Franz Steppeler ◽

Dominika Iwan ◽

Elżbieta Wojaczyńska ◽

Jacek Wojaczyński

Keyword(s):

Hydrogen Bond ◽

Drug Development ◽

Asymmetric Synthesis ◽

Stereoselective Synthesis ◽

Strong Hydrogen Bond ◽

Hydrogen Bond Donor ◽

Drug Candidates ◽

Current State ◽

The Family ◽

Donor Capability

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development.

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One-pot stereoselective synthesis of β-N-aryl-glycosides by N-glycosylation of aromatic amines: application to the synthesis of tumor-associated carbohydrate antigen building blocks

Tetrahedron ◽

10.1016/j.tet.2007.02.092 ◽

2007 ◽

Vol 63 (19) ◽

pp. 4178-4183 ◽

Cited By ~ 21

Author(s):

Nicolas Bridiau ◽

Moulay Benmansour ◽

Marie Dominique Legoy ◽

Thierry Maugard

Keyword(s):

Aromatic Amines ◽

Stereoselective Synthesis ◽

Building Blocks ◽

Carbohydrate Antigen ◽

One Pot ◽

Aryl Glycosides

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Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

Frontiers in Immunology ◽

10.3389/fimmu.2021.642383 ◽

2021 ◽

Vol 12 ◽

Author(s):

José T. Moreira-Filho ◽

Arthur C. Silva ◽

Rafael F. Dantas ◽

Barbara F. Gomes ◽

Lauro R. Souza Neto ◽

...

Keyword(s):

Artificial Intelligence ◽

Drug Discovery ◽

Cost Effective ◽

Neglected Tropical Disease ◽

Parasitic Disease ◽

Drug Candidates ◽

Single Drug ◽

Computer Aided ◽

Prevalent Disease ◽

Effective Drugs

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.

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Coronavirus Disease 2019 (COVID-19): Origin, Impact, and Drug Development

10.5772/intechopen.98358 ◽

2021 ◽

Author(s):

Amaresh Mishra ◽

Nisha Nair ◽

Amit K. Yadav ◽

Pratima Solanki ◽

Jaseela Majeed ◽

...

Keyword(s):

Vaccine Development ◽

Therapeutic Option ◽

Treatment Strategies ◽

Drug Repurposing ◽

Cost Effective ◽

High Sequence Identity ◽

Drug Candidates ◽

Global Pandemic ◽

The People ◽

Health Organization

At the end of December 2019, in Wuhan, China, a rapidly spreading unknown virus was reported to have caused coronavirus disease of 2019 (COVID-19). Origin linked to Wuhan’s wholesale food market where live animals are sold. This disease is caused by SARS Coronavirus-2 (SARS-CoV-2), which is closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This virus shares a high sequence identity with bat-derived SARS-like Coronavirus, which indicating its zoonotic origin. The virus spread globally, provoking widespread attention and panic. This Coronavirus is highly pathogenic and causes mild to severe respiratory disorders. Later, it was declared a global pandemic by the World Health Organization (WHO) due to its highly infectious nature and worldwide mortality rate. This virus is a single-stranded, positive-sense RNA genome, and its genome length about 26 to 32 kb that infects a broad range of vertebrates. The researchers worldwide focus on establishing treatment strategies on drug and vaccine development to prevent this COVID-19 pandemic. A drug repurposing approach has been used to identify a rapid treatment for the people affected by COVID-19, which could be cost-effective and bypass some Food and Drug Association (FDA) regulations to move quickly in phase-3 trials. However, there is no promising therapeutic option available yet. This book chapter addresses current information about the COVID-19 disease, including its origins, impacts, and the novel potential drug candidates that can help treat the COVID-19.

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Label-Free Bioelectrochemical Methods for Evaluation of Anticancer Drug Effects at a Molecular Level

Sensors ◽

10.3390/s20071812 ◽

2020 ◽

Vol 20 (7) ◽

pp. 1812 ◽

Cited By ~ 3

Author(s):

Francesco Tadini-Buoninsegni ◽

Ilaria Palchetti

Keyword(s):

Anticancer Drugs ◽

Anticancer Drug ◽

Drug Effects ◽

Cost Effective ◽

Research Area ◽

Screening Methods ◽

Label Free ◽

Supported Membranes ◽

Drug Candidates ◽

Novel Drug

Cancer is a multifactorial family of diseases that is still a leading cause of death worldwide. More than 100 different types of cancer affecting over 60 human organs are known. Chemotherapy plays a central role for treating cancer. The development of new anticancer drugs or new uses for existing drugs is an exciting and increasing research area. This is particularly important since drug resistance and side effects can limit the efficacy of the chemotherapy. Thus, there is a need for multiplexed, cost-effective, rapid, and novel screening methods that can help to elucidate the mechanism of the action of anticancer drugs and the identification of novel drug candidates. This review focuses on different label-free bioelectrochemical approaches, in particular, impedance-based methods, the solid supported membranes technique, and the DNA-based electrochemical sensor, that can be used to evaluate the effects of anticancer drugs on nucleic acids, membrane transporters, and living cells. Some relevant examples of anticancer drug interactions are presented which demonstrate the usefulness of such methods for the characterization of the mechanism of action of anticancer drugs that are targeted against various biomolecules.

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