1.
Angew Chem Int Ed Engl
; 54(5): 1551-5, 2015 Jan 26.
Artigo
em Inglês
| MEDLINE
| ID: mdl-25475886
RESUMO
We report a multi-objective deâ novo design study driven by synthetic tractability and aimed at the prioritization of computer-generated 5-HT2B receptor ligands with accurately predicted target-binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand-efficient 5-HT2B modulators with sustained cell-based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics-assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.