Obiettivo Modern drug discovery is facing critical challenges. Rapid advances in human biology are revealing new biomolecular targets and processes, for which existing chemical compound libraries can provide only limited success in the identification of novel bioactive agents. This deficiency has been attributed primarily to the relative lack of structural diversity within the libraries. The three-dimensional world of biological macromolecules has been continuously interrogated with generally similar planar, aromatic, and structurally simple compounds. Contemporary diversity-generating methods have never been implemented for the preparation of large libraries, as an increase in the number of diverse members requires a corresponding increase in the number of synthetic steps, or a continuous supply of different staring materials. This proposal details a strategy for developing a chemically sustainable diversification method, by tapping into our largest source of organic compounds: arenes.The proposed research aims to develop new methods that can rapidly convert simple aromatic entities into highly functionalized, complex small molecules. By integration of this strategy with many different chemical operations, numerous distinctive and independent dearomative programs will generate a diverse set of multiplex small molecules. This simplicity-to-complexity approach will provide a practical platform for the rapid, controlled access to a functionally diverse set of compounds, ranging from anticancer to anti-infective agents. This research will also deliver methods for dearomative diversification of existing aromatic compound libraries to provide new members with unique physiochemical properties. Given the broad scope of possible dearomative programs that will be developed, and the vast amount of aromatic compounds accessible, this will ultimately provide a sustainable source of diverse molecules for the next generation of compound libraries. Campo scientifico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural scienceschemical sciencesorganic chemistryhydrocarbonsnatural scienceschemical sciencesorganic chemistryaromatic compounds Parole chiave Drug discovery drug design chemical diversity sustainability medicinal chemistry organic synthesis dearomatization Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2018-STG - ERC Starting Grant Invito a presentare proposte ERC-2018-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Istituzione ospitante UNIVERSITA DEGLI STUDI DI PAVIA Contribution nette de l'UE € 1 400 000,00 Indirizzo STRADA NUOVA 65 27100 Pavia Italia Mostra sulla mappa Regione Nord-Ovest Lombardia Pavia Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 400 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNIVERSITA DEGLI STUDI DI PAVIA Italia Contribution nette de l'UE € 1 400 000,00 Indirizzo STRADA NUOVA 65 27100 Pavia Mostra sulla mappa Regione Nord-Ovest Lombardia Pavia Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 400 000,00
