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  • Universidade de Lisboa: Repositório.UL

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  • Restricted English
    Authors: 
    Rodrigues, Marina;
    Country: Portugal

    Flow Chemistry is a powerful tool in organic synthesis. It provides great operational advantages such as process intensification, access to new chemical space, efficient mass and heat transfers, straightforward scalability, and increased yields. These distinctive advantages were considered during the process chemistry development of active pharmaceutical ingredients very sensitive to light and oxygen. Within this doctoral thesis, continuous methodologies were employed in a 4-step process to obtain an antibiotic drug urgently needed for the treatment of community-acquired bacterial pneumonia. The process was developed and optimized based on previously described batch procedures found in the literature. Looking at the processes described, it was clear that Flow Chemistry could bring significant advantages, for a product already in the market with a defined batch process. Advantages such as the non-isolation of sensitive intermediates, increase of selectivity and consequently the yield, and reduction of impurities certainly are worth the bureaucratic burden associated with major process changes. Careful selection of the continuous flow equipment and integration of common lab material in handmade setups enabled the preparation process intermediates and final product in a telescoped manner. Downstream unit operations such as distillation and nanofiltration were operated under semi-continuous mode. Mechanistic (Dynochem) and empiric (DoE) modeling were applied for process optimization and design space determination reducing the development time and increasing process knowledge. Implementation of Process Analytical Technology (PAT) allowed greater process understanding and monitoring. Control charts were built to anticipate the impact of equipment malfunctions on the quality of the reaction mixtures. Also, the use of PAT provides a fast-decision-making approach without having to wait for In-Process Control (IPC) analysis such as High-Performance Liquid Chromatography (HPLC). Process intensification enabled by flow chemistry resulted in a reduction of one chemical step, higher global yield, and fewer downstream operations than the process described in the literature.

  • Restricted English
    Authors: 
    Silva, Gustavo Da;
    Country: Portugal

    Despite excellent drug discovery programs and unprecedent commitment to eliminate malaria, this protozoan disease remains a major cause of mortality and morbidity worldwide, and specially in developing nations. Apart from socio-economic issues, drug-resistance seems to be the major causing factor for the malaria incidence in these countries. This project aimed to disclose new leads that are active against drug-resistant malaria parasites, acting as multi-stage antimalarials with new mechanisms of action (MoA). A common synthetic strategy was explored to prepare new chemical entities (NCE) and structurally related heterocycles, which included the synthesis of indoles, quinolones and spiroindolones. A library of pyrroloquinolones was prepared based on the Winterfeldt chemistry. The Winterfeldt precursors were usually prepared based on Pictet-Spengler reactions, followed by N-acylation or N-alkylation. A pyrroloquinolone lead was disclosed from this small library, with nanomolar antimalarial activity, against blood-stage and liver stage parasites. The lead compound revealed to be a DHODH and cytochrome bc1 inhibitor, targeting two components of the plasmodial mitochondrial electron transport chain, and favorable pharmacokinetic properties. The lead compound also revealed to be stable (absence of putative hydroxylated metabolites), after incubation with human and mouse liver microsomes. A secondary library of polyfunctionalized indoles was prepared via A3 coupling of aldehydes, amines and alkynes. The exploratory project that aimed for the diversity-oriented synthesis of novel pyrroloquinoles yielded a synthetic intermediate with low sub-micromolar antimalarial activity against drug-sensitive and drug-resistant blood stage malaria parasites with unknown MoA, which has an inhibitory activity comparable to the most potent indole antimalarials known. The lead compound from this library enabled systemic exposure after oral administration and limited aqueous kinetic solubility. A tertiary library of spiroindolones was also prepared, using previously prepared Winterfeldt precursors. The extension of this preliminary strategy of repurposing tetrahydro-ß-carbolines as synthetic intermediates for oxidative rearrangement yielded unprecedented antimalarial spiroindolones with nanomolar activity against drug-sensitive and drug-resistant blood-stage malaria parasites. This project was a contribution for the development of three small libraries of synthetically related N-containing heterocycles, with promising antimalarial activity.

  • Other research product . 2022
    Restricted English
    Authors: 
    Liz, Mariana;
    Publisher: Routledge. Taylor and Francis
    Country: Portugal

    In Wim Wenders’ Lisbon Story (1994), a German sound engineer travels from Frankfurt to Lisbon to help a friend finish a film about the city. Lisbon is at once traditional and modern. Blue sunny skies, the reflecting waters of the river and the narrow alleys of the historical center are beautifully framed and matched in the soundtrack by the melancholic music of Madredeus. The film invites to the city the tourists that hadn’t yet arrived while highlighting the material and economic progress still to come. Flash-forward 20 years, to Night Train to Lisbon (Bille August, 2013): the light inundates the frame and presents us with a more preserved, picture-perfect Lisbon. It is full of visitors and free of scaffolding, yet still very much attached to its past. If Lisbon Story was made for a niche audience, Night Train to Lisbon had over 1.5 million viewers across Europe. Whereas Lisbon Story was one of the few films shot in Lisbon in the 1990s, Night Train to Lisbon is part of a wider media landscape and was filmed at a time when the city had become the setting for Bollywood productions, German TV series and the music video for Shakira’s 2014 single Dare. In June 2018, the Portuguese government approved a cash rebate scheme to encourage the shooting of audiovisual productions in Portugal. As the number of visitors to the Portuguese capital continues to grow, and this growth is matched by increasing filming permit requests, what is Lisbon’s international screen image?

  • Restricted Spanish; Castilian
    Authors: 
    Truninger, Monica; Ramos, Vasco;
    Publisher: Tirant humanidades
    Country: Portugal
  • Other research product . 2022
    Restricted Portuguese
    Authors: 
    Marques, António Pedro;
    Publisher: Faculdade de Belas-Artes da Universidade de Lisboa
    Country: Portugal
  • Other research product . 2022
    Restricted English
    Authors: 
    Silva, Filipe Carreira da;
    Publisher: Ministerio de Derechos Sociales y Agenda 2030
    Country: Portugal

    Since 2002, youth has become more important on the European agenda and in recent years has become one of the central issues that need addressing in order to shape Europe's future. In the 2021 State of the Union address, the President of the European Commission, Ursula Von der Leyen, endorsed this priority with the formal adoption of the "European Year of Youth" and again in her 2022 speech, the President stated that the aspirations of Europe's youth should be at the heart of everything Europe does. This strategic priority represents recognition of the sacrifices and challenges that young Europeans have faced during the Covid-19 crisis, which have been exacerbated as a consequence of the war in Ukraine. This second global crisis has occurred in a very short period of time after the 2008 economic crisis, leaving an even more significant impression on a generation that is now entering its youth. This context of a lack of opportunities is determining the present and conditioning the future.

  • Restricted English
    Authors: 
    Fraga, Joana;
    Publisher: Brill
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Reis, Jorge dos;
    Publisher: Faculdade de Belas Artes da Universidade de Lisboa
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Quaresma Pedro, José;
    Publisher: Faculdade de Belas-Artes da Universidade de Lisboa
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Rodrigues, Nuno Simões;
    Publisher: Desalinho
    Country: Portugal

    Este estudo analisa a «Laudatio Turiae», usando-a como fonte para o estudo da criação de um modelo feminino na Roma do fim da República e início do Principado.

Advanced search in
Research products
arrow_drop_down
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arrow_drop_down
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Include:
3,968 Research products, page 1 of 397
  • Restricted English
    Authors: 
    Rodrigues, Marina;
    Country: Portugal

    Flow Chemistry is a powerful tool in organic synthesis. It provides great operational advantages such as process intensification, access to new chemical space, efficient mass and heat transfers, straightforward scalability, and increased yields. These distinctive advantages were considered during the process chemistry development of active pharmaceutical ingredients very sensitive to light and oxygen. Within this doctoral thesis, continuous methodologies were employed in a 4-step process to obtain an antibiotic drug urgently needed for the treatment of community-acquired bacterial pneumonia. The process was developed and optimized based on previously described batch procedures found in the literature. Looking at the processes described, it was clear that Flow Chemistry could bring significant advantages, for a product already in the market with a defined batch process. Advantages such as the non-isolation of sensitive intermediates, increase of selectivity and consequently the yield, and reduction of impurities certainly are worth the bureaucratic burden associated with major process changes. Careful selection of the continuous flow equipment and integration of common lab material in handmade setups enabled the preparation process intermediates and final product in a telescoped manner. Downstream unit operations such as distillation and nanofiltration were operated under semi-continuous mode. Mechanistic (Dynochem) and empiric (DoE) modeling were applied for process optimization and design space determination reducing the development time and increasing process knowledge. Implementation of Process Analytical Technology (PAT) allowed greater process understanding and monitoring. Control charts were built to anticipate the impact of equipment malfunctions on the quality of the reaction mixtures. Also, the use of PAT provides a fast-decision-making approach without having to wait for In-Process Control (IPC) analysis such as High-Performance Liquid Chromatography (HPLC). Process intensification enabled by flow chemistry resulted in a reduction of one chemical step, higher global yield, and fewer downstream operations than the process described in the literature.

  • Restricted English
    Authors: 
    Silva, Gustavo Da;
    Country: Portugal

    Despite excellent drug discovery programs and unprecedent commitment to eliminate malaria, this protozoan disease remains a major cause of mortality and morbidity worldwide, and specially in developing nations. Apart from socio-economic issues, drug-resistance seems to be the major causing factor for the malaria incidence in these countries. This project aimed to disclose new leads that are active against drug-resistant malaria parasites, acting as multi-stage antimalarials with new mechanisms of action (MoA). A common synthetic strategy was explored to prepare new chemical entities (NCE) and structurally related heterocycles, which included the synthesis of indoles, quinolones and spiroindolones. A library of pyrroloquinolones was prepared based on the Winterfeldt chemistry. The Winterfeldt precursors were usually prepared based on Pictet-Spengler reactions, followed by N-acylation or N-alkylation. A pyrroloquinolone lead was disclosed from this small library, with nanomolar antimalarial activity, against blood-stage and liver stage parasites. The lead compound revealed to be a DHODH and cytochrome bc1 inhibitor, targeting two components of the plasmodial mitochondrial electron transport chain, and favorable pharmacokinetic properties. The lead compound also revealed to be stable (absence of putative hydroxylated metabolites), after incubation with human and mouse liver microsomes. A secondary library of polyfunctionalized indoles was prepared via A3 coupling of aldehydes, amines and alkynes. The exploratory project that aimed for the diversity-oriented synthesis of novel pyrroloquinoles yielded a synthetic intermediate with low sub-micromolar antimalarial activity against drug-sensitive and drug-resistant blood stage malaria parasites with unknown MoA, which has an inhibitory activity comparable to the most potent indole antimalarials known. The lead compound from this library enabled systemic exposure after oral administration and limited aqueous kinetic solubility. A tertiary library of spiroindolones was also prepared, using previously prepared Winterfeldt precursors. The extension of this preliminary strategy of repurposing tetrahydro-ß-carbolines as synthetic intermediates for oxidative rearrangement yielded unprecedented antimalarial spiroindolones with nanomolar activity against drug-sensitive and drug-resistant blood-stage malaria parasites. This project was a contribution for the development of three small libraries of synthetically related N-containing heterocycles, with promising antimalarial activity.

  • Other research product . 2022
    Restricted English
    Authors: 
    Liz, Mariana;
    Publisher: Routledge. Taylor and Francis
    Country: Portugal

    In Wim Wenders’ Lisbon Story (1994), a German sound engineer travels from Frankfurt to Lisbon to help a friend finish a film about the city. Lisbon is at once traditional and modern. Blue sunny skies, the reflecting waters of the river and the narrow alleys of the historical center are beautifully framed and matched in the soundtrack by the melancholic music of Madredeus. The film invites to the city the tourists that hadn’t yet arrived while highlighting the material and economic progress still to come. Flash-forward 20 years, to Night Train to Lisbon (Bille August, 2013): the light inundates the frame and presents us with a more preserved, picture-perfect Lisbon. It is full of visitors and free of scaffolding, yet still very much attached to its past. If Lisbon Story was made for a niche audience, Night Train to Lisbon had over 1.5 million viewers across Europe. Whereas Lisbon Story was one of the few films shot in Lisbon in the 1990s, Night Train to Lisbon is part of a wider media landscape and was filmed at a time when the city had become the setting for Bollywood productions, German TV series and the music video for Shakira’s 2014 single Dare. In June 2018, the Portuguese government approved a cash rebate scheme to encourage the shooting of audiovisual productions in Portugal. As the number of visitors to the Portuguese capital continues to grow, and this growth is matched by increasing filming permit requests, what is Lisbon’s international screen image?

  • Restricted Spanish; Castilian
    Authors: 
    Truninger, Monica; Ramos, Vasco;
    Publisher: Tirant humanidades
    Country: Portugal
  • Other research product . 2022
    Restricted Portuguese
    Authors: 
    Marques, António Pedro;
    Publisher: Faculdade de Belas-Artes da Universidade de Lisboa
    Country: Portugal
  • Other research product . 2022
    Restricted English
    Authors: 
    Silva, Filipe Carreira da;
    Publisher: Ministerio de Derechos Sociales y Agenda 2030
    Country: Portugal

    Since 2002, youth has become more important on the European agenda and in recent years has become one of the central issues that need addressing in order to shape Europe's future. In the 2021 State of the Union address, the President of the European Commission, Ursula Von der Leyen, endorsed this priority with the formal adoption of the "European Year of Youth" and again in her 2022 speech, the President stated that the aspirations of Europe's youth should be at the heart of everything Europe does. This strategic priority represents recognition of the sacrifices and challenges that young Europeans have faced during the Covid-19 crisis, which have been exacerbated as a consequence of the war in Ukraine. This second global crisis has occurred in a very short period of time after the 2008 economic crisis, leaving an even more significant impression on a generation that is now entering its youth. This context of a lack of opportunities is determining the present and conditioning the future.

  • Restricted English
    Authors: 
    Fraga, Joana;
    Publisher: Brill
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Reis, Jorge dos;
    Publisher: Faculdade de Belas Artes da Universidade de Lisboa
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Quaresma Pedro, José;
    Publisher: Faculdade de Belas-Artes da Universidade de Lisboa
    Country: Portugal
  • Restricted Portuguese
    Authors: 
    Rodrigues, Nuno Simões;
    Publisher: Desalinho
    Country: Portugal

    Este estudo analisa a «Laudatio Turiae», usando-a como fonte para o estudo da criação de um modelo feminino na Roma do fim da República e início do Principado.

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