Integrated Ugi-Based Assembly of Functionally, Skeletally, and Stereochemically Diverse 1,4-Benzodiazepin-2-ones

A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2-ones exhibiting functionally, skeletally, and stereochemically diverse substitution patterns is described. By virtue of its convergence, atom economy, and bond-forming efficiency, the methodology documented herein exemplifies the reconciliation of structural complexity and experimental simplicity in the context of medicinal chemistry projects.This work was financially supported by the Galician Government (Spain), Projects: 09CSA016234PR and GPC-2014-PG037. J.A. thanks FUNDAYACUCHO (Venezuela) for a predoctoral grant and Deputación da Coruña (Spain) for a postdoctoral research grant. A.N.-V. thanks the Spanish government for a Ramón y Cajal research contract

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Cationic Host Defence Peptides:Potential as Antiviral Therapeutics

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics

Proposal of a Validation Method for Automated Nucleic Acid Extraction and RT -qPCR Analysis: an Example with Bluetongue Virus

Resumen en inglès, ver archivo PD

Emergence of Bluetongue Virus Serotypes in Europe. Part I. Description and Validation of Four Real-Time RT-PCR Assays

Resumen en inglès, ver archivo PD

The use of serosurveys following emergency vaccination, to recover the status of "foot-and-mouth disease free where vaccination is not practised"

To eliminate incursions of foot-and-mouth disease (FMD) quickly, a combination of measures, including emergency vaccination, can help block the spread of infection. For the earliest recovery of the FMD-free status for trade, without the slaughter of uninfected vaccinated animals, a serosurvey for antibodies to FMD virus non-structural proteins (NSP) must be used to substantiate absence of occult virus infections. Areas of doubt over requirements for post-vaccination serosurveillance and its feasibility include the required and achievable confidence, the amount of sampling necessary, and the appropriate responses to and consequences of different seropositive findings. This derives largely from uncertainty over the extent of localised pockets of virus infection that may remain within vaccinated populations and the circumstances that permit this. The question therefore remains whether tests are sufficiently sensitive and specific to detect and eliminate infected animals, without excessive culling of uninfected animals, before vaccinated animals mix with non-vaccinated livestock when movement restrictions are lifted. It is recommended to change the rationale for serosurveillance after emergency vaccination. Only when emergency vaccination is used in limited outbreaks is it possible to test and cull comprehensively, an approach compatible with a three-month minimum period to recover the FMD-free status. In other situations, where emergency vaccination is used, such as dealing with large outbreaks in animal-dense regions and where the onset of vaccination has been delayed, post-vaccination serosurveys should be targeted and focus on providing an assurance to detect higher levels of infection, in case of inadequate control measures. As this provides less assurance of absence of infection, the approach would be compatible with a six-month waiting period for free-status recovery and should be complemented by other methods to provide evidence that vaccination and control measures have been effectively implemented, as these are the best guarantee against continuing virus transmission