Descrizione del progetto
Un’innovativa tecnologia chimica apre un nuovo capitolo nella scoperta di farmaci
L’anello di ciclopropano è un gruppo chimico composto da tre gruppi di metilene uniti assieme in un triangolo e viene spesso inserito in farmaci con piccole molecole nelle prime fasi della sintesi per migliorarne la stabilità metabolica, la conformazione e la farmacocinetica. Il progetto LateCPC, finanziato dall’UE, si propone di sviluppare un metodo innovativo che generi ciclopropani a partire da legami carbonio-idrogeno e possa dunque essere utilizzato per la sintesi di farmaci complessi. Oltre ad ampliare l’applicabilità dell’anello di ciclopropano nella chimica farmaceutica, questo metodo dovrebbe affrontare le esigenze mediche non soddisfatte attraverso la scoperta di nuovi farmaci.
Obiettivo
The cyclopropane ring is the 10th most commonly observed core in small-molecule drugs. This is due to the fact that cyclopropanes can positively influence metabolic stability, conformation, pKa, entropy, membrane permeability or pharmacokinetics in drug leads. The cyclopropane ring is often introduced in drug candidates at the early stages of the synthesis, however, the late-stage construction of multi-substituted cyclopropanes using C–H bonds as a functional group has not been developed yet. This concept promise to reach a “cyclopropanated” chemical space not possible by current strategies and that may impact how medicinal chemists will discover cyclopropane-based drugs that address unmet medical needs. LateCPC aims to develop an innovative technology to rapidly construct cyclopropanes from C–H bonds in feedstock and fine aromatic molecules as well as in complex drug molecules. Our approach will rely on the diazo activation of bespoke carbyne sources developed in the host group with metal catalysts, allowing the catalytic generation of metal-carbynoids. A key strength of this conceptually new and multidisciplinary proposal is the introduction of a secondment phase in Novartis (Basel) to explore real-life applications. The ambitious action merges perfectly the expertise of the host in novel C−H functionalization strategies based on the catalytic generation of innovative carbyne equivalents with the strong background of the applicant in metal-catalyzed Tsuji-Trost reactions, thus enhancing two-way transfer of knowledge between the ER and the host group. Successful development of this project will enable the ER to become a leader for the next generation in the field of chemical synthesis and late-stage functionalization techniques. The ER will be exposed to a wide range of cutting-edge chemistry and biomedical sciences in an interdisciplinary and international environment (ICIQ) that will aid the fellow’s competencies and cultivate him as independent researcher.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
43007 Tarragona
Spagna