1,721,003 research outputs found
Integrated Synthetic Platforms for Chemical Probes: A Journey through the Routes of Flow Processing
No full textThe talk will focus on our recent efforts directed towards the design and implementation of integrated flow platforms for the production of chemical probes and compound library in drug discovery programmes
Set-up and assessment of flow systems for streamlined synthesis and medicinal chemistry
No full textOver the past two decades, the advent of technological innovation in synthesis has been of crucial importance to fulfil the criteria and needs of modern drug discovery. Novel concepts and strategies have been adopted to enable the rapid assembly of compounds collections available for screenings and the production of clinical candidates to support in vivo efficacy and safety testing. Among chemical technologies, continuous flow chemistry has proven particularly suitable for these purposes offering new solutions and several advantages over more traditional approaches. The ability to easily scale-up reactions led to a major impact of flow systems on the development of lead compounds reducing re-synthesis times, and most recently being further applied to manufacturing processes of marketed drugs.
This talk deals with the set-up and implementation of flow strategies designed to accelerate the total compound generation for the biological screening of druggable targets, as well as with the optimization of multistep flow processes for the preparation of lead compounds to be advanced in (pre)clinical studies (Figure 1). The integration of continuous flow synthesis with computational tools, automated purifications, and in-line analysis will be exemplified by case studies that show the potential of these systems to improve performance, product quality and throughput, automation, safety standards with the concomitant reductions in cost and waste generation
Enabling Synthetic Technologies for Chemical Libraries, Hit Optimization and Scale-up: In-flow Synthesis and Biological Activity of Quinoline-based Compounds
No full textIn the changing landscape of drug discovery, technological innovation in synthesis is playing a crucial role from early phase of lead identification to production. Nowadays, synthetic strategies are designed to be versatile for a fast access to chemical libraries and, at the same time, easily scalable to support in vivo efficacy, safety testing, and clinical trials. The increasing number of reports and publications, the capital investments of pharmaceutical industries, and the availability of commercial equipments are qualifying continuous flow technology particularly suitable for these purposes. The potential advantages of the flow chemistry include high control of the reaction variables, which can translate into higher product quality; increased safety and ecosustainability; possibility of conduct reactions at supercritical conditions; feasibility of automation reducing manual handling and accelerating products throughput; reproducibility and easy scale-up; possibility of in-line purification, analysis and reaction telescoping; process intensification resulting in a smaller footprint in a manufacturing plant.
In this communications, our recent efforts directed towards the set-up and implementation of integrated flow platforms developed to accelerate the total compound-generation, to improve chemical processes, as well as to decrease the instrument face time by the operating scientist, will be presented. In particular, the prototype systems will be exemplifyed by case studies within our medicinal chemistry programmes showing the potential to reduce significantly the time and cost of preclinical drug discovery
Future medicinal chemists experience flow chemistry: optimization by experimental design of the limiting synthetic step to the antifungal drug econazole nitrate
No full textA practical experience to showcase the potential of flow technology in the synthesis optimization of drugs has been developed and carried out by fourth year undergraduate students in Pharmaceutical Chemistry and Technology (CTF) at the University of Perugia. In particular, we present an experiment aimed at optimizing the monobromination reaction of 2′,4′-dichloroacetophenone, the limiting step to the synthesis of the antifungal drug econazole nitrate. Throughout the experiment, the students learn how to integrate flow chemistry and experimental design to expedite experimental screening and reaction optimization. Moreover, the students have the possibility to exploit the use of automation to improve data generation and reduce human intervention in repetitive, expensive or hazardous experiments
The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology
Full text linkMedicinal chemistry plays a fundamental and underlying role in chemical biology, pharmacology, and medicine to discover safe and efficacious drugs. Small molecule medicinal chemistry relies on iterative learning cycles composed of compound design, synthesis, testing, and data analysis to provide new chemical probes and lead compounds for novel and druggable targets. Using traditional approaches, the time from hypothesis to obtaining the results can be protracted, thus limiting the number of compounds that can be advanced into clinical studies. This challenge can be tackled with the recourse of enabling technologies that are showing great potential in improving the drug discovery process. In this Perspective, we highlight recent developments toward innovative medicinal chemistry strategies based on continuous flow systems coupled with automation and bioassays. After a discussion of the aims and concepts, we describe equipment and representative examples of automated flow systems and end-to-end prototypes realized to expedite medicinal chemistry discovery cycles
Recent advances in urea- And thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis
No full textUrea and thiourea represent privileged structures in medicinal chemistry. Indeed, these moieties constitute a common framework of a variety of drugs and bioactive compounds endowed with a broad range of therapeutic and pharmacological properties. Herein, we provide an overview of the state-of-the-art of urea and thiourea-containing pharmaceuticals. We also review the diverse approaches pursued for (thio)urea bioisosteric replacements in medicinal chemistry applications. Finally, representative examples of recent advances in the synthesis of urea- and thiourea-based compounds by enabling chemical tools are discussed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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