Synthetic toolkit for fragment oriented synthesis

Información del proyecto

SYNFOS

Identificador del acuerdo de subvención: 795189

DOI

10.3030/795189

Proyecto finalizado el 30 Agosto 2019

Fecha de la firma de la CE 20 Febrero 2018

Fecha de inicio 1 Marzo 2018

Fecha de finalización 29 Febrero 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 195 454,80

Aportación de la UE

€ 195 454,80

Coordinado por

UNIVERSITY OF LEEDS
United Kingdom

Objetivo

Fragment-based ligand discovery (FBLD) has become a mainstream strategy to discover new drugs to enable the treatment of conditions with unmet medical needs. Despite the remarkable rise of FBLD, significant chemical challenges remain in the field; firstly, elaborated fragments tend to be synthesised de novo when direct growth would be much more advantageous. Secondly, the currently available toolkit for fragment elaboration tends to exacerbate an uneven exploration of chemical space, yielding flatter and more lipophilic compounds.

SYNFOS will allow Alexandre Trindade (the fellow) to join the laboratory of Professors Adam Nelson (host supervisor) and Steve Marsden (host co-supervisor) at the University of Leeds (Host) and develop research expertise in fragment-based ligand discovery; catalysis to enable molecular discovery; protein-protein interaction (PPIs) inhibition; and high-throughput X-ray crystallography (via secondments to Diamond (Partner)). In doing so, the fellow will (a) enhance his prospects of becoming an independent academic group leader in Europe and (b) address the need to train researchers in key multidisciplinary areas such as medicinal chemistry and chemical biology and (c) develop cutting edge synthetic methods that facilitates the fragment-based discovery of new inhibitors for protein-protein interactions. By building in fragment hits from the Host laboratory, the fellow will establish a synthetic toolkit enabling the functionalization of C-H bonds within N-heterocycles with a wide range of medicinally-relevant groups. The fellowship will explore three main modes of reactivity to establish the functionalization of sp3-hydridised carbons with heterocyclic fragments and showcase the value of the synthetic toolbox through the discovery of fragments hits into potent inhibitors of PPIs involving the ATAD2 bromodomain.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › medicina básica › farmacología y farmacia › descubrimiento de fármacos
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas › proteómica
• ciencias médicas y de la salud › medicina básica › química medicinal
• ciencias naturales › ciencias de la tierra y ciencias ambientales conexas › geología › mineralogía › cristalografía
• ciencias naturales › ciencias químicas › catálisis

Palabras clave

• fragment-based ligand discovery
• photoredox catalysis
• metallocarbenoid chemistry
• inhibitors of protein-protein interactions

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2017 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2017

Coordinador

UNIVERSITY OF LEEDS

• Aportación neta de la UEn: € 195 454,80
• Dirección: WOODHOUSE LANE ; LS2 9JT Leeds ; Reino Unido
• Región: Yorkshire and the Humber › West Yorkshire › Leeds
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 195 454,80