Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Май 26, 2025
During multiparameter chemical optimization, molecular capabilities increase as hits evolve into leads and development candidates. Like retrosynthetic analysis, where target molecules are transformed structurally simplified starting materials, we introduce retro-optimization transforming sophisticated candidates less capable hits. To retrospectively understand the logic of optimization in discovery campaigns, enumerated a matched pair network compared actual route taken to alternative theoretical routes optimization. We noted differences properties lead molecule those alternatives. identified substructures evolving ligand, named "optimizons," tracked their emphasis discovery. While initially defined illustrated these methods for single project, our expansion three additional projects external data sets proved consistent. define at molecular, submolecular levels prospectively guide current future campaigns.
Язык: Английский