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

'Embrace the masculine; attenuate the feminine': gender, identity work and entrepreneurial legitimation in the nascent context

This paper critically analyses how gender bias impacts upon women’s efforts to legitimate nascent ventures. Given the importance of founder identity as a proxy for entrepreneurial legitimacy at nascency, we explore the identity work women undertake when seeking to claim legitimacy for their emerging ventures in a prevailing context of masculinity. In so doing, we challenge taken for granted norms pertaining to legitimacy and question the basis upon which that knowledge is claimed. In effect, debates regarding entrepreneurial legitimacy are presented as gender neutral yet, entrepreneurship is a gender biased activity. Thus, we argue it is essential to recognise how gendered assumptions impinge upon the quest for legitimacy. To illustrate our analysis, we use retrospective and real time empirical evidence evaluating legitimating strategies as they unfold, our findings reveal tensions between feminine identities such as ‘wife’ and ‘mother’ and those of the prototypical entrepreneur. This dissonance prompted women to undertake specific forms of identity work to bridge the gap between femininity, legitimacy and entrepreneurship. We conclude by arguing that the pursuit of entrepreneurial legitimacy during nascency is a gendered process which disadvantages women and has the potential to negatively impact upon the future prospects of their fledging ventures

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

Prevalence and risk factors of Hypoglycemia in virulent\ud Canine Babesiosis

Hypoglycemia is a common complication of virulent canine babesiosis. A study was conducted to determine the prevalence of and potential risk factors for hypoglycemia in canine babesiosis from Babesia canis rossi. Plasma glucose concentration was measured at presentation in 250 dogs with babesiosis, of which 111 were admitted to hospital. The prevalence of hypoglycemia (<60 mg/ dL) was 9% (23/250). Twenty-two hypoglycemic dogs required admission, making the prevalence of hypoglycemia in admitted dogs 19.8%. Sixteen dogs had severe hypoglycemia (<40 mg/dL), of which 5 had glucose < 18 mg/dL. Hyperglycemia (>100 mg/dL) was present in 38 dogs, of which 21 were admitted. Risk factors for hypoglycemia identified by univariate analysis were collapsed state (P < .00001), severe anemia (P= .0002), icterus (P= .003), age <6 months (P= .02), and vomiting (P= .03). After logistic regression analysis, collapsed state (odds ratio [OR] = 18; 95% CI, 1.9–171; P= .01) and young age (OR = 2.8; 95% CI, 0.8–9.7; P = .1) remained significantly associated with hypoglycemia. Toy breeds and pregnant bitches were not at higher risk for hypoglycemia than other dogs. Blood glucose concentration should ideally be measured in all dogs requiring inpatient treatment for babesiosis but is mandatory in collapsed dogs; puppies; and dogs with severe anemia, vomiting, or icterus. Many dogs have probably been misdiagnosed with cerebral babesiosis in the past, and hypoglycemia should be suspected in any dog with coma or other neurological signs