title: Assessing molecular scaffolds for CNS drug discovery.
abstract: There is a need for high-quality screening collections that maximise hit rate and minimise the time taken in lead optimisation to derive a candidate drug. Identifying and accessing molecules that meet these criteria is a challenge. Within central nervous system (CNS)-focused drug discovery, this challenge is heightened by the requirement for lead compounds to cross the blood-brain barrier. Herein, we demonstrate use of a multiparameter optimisation tool to prioritise the synthesis of molecular scaffolds that, when subsequently decorated, yield screening compounds with experimentally determined properties that align with CNS lead generation needs. Prospective use of this CNS Lead Multiparameter Optimisation (MPO) scoring protocol can guide the further development of novel synthetic methodologies to access CNS-relevant and lead-like chemical space.
authors.affiliation: School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Joan
authors.initials: J
authors.lastname: Mayol-Llinàs
authors.affiliation: School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. Electronic address: A.S.Nelson@leeds.ac.uk.
authors.forename: Adam
authors.initials: A
authors.lastname: Nelson
authors.affiliation: Takeda Cambridge, Unit 418, Cambridge Science Park, Milton Road, Cambridge CB4 0PA, UK. Electronic address: w.farnaby@dundee.ac.uk.
authors.forename: William
authors.initials: W
authors.lastname: Farnaby
authors.affiliation: Takeda Cambridge, Unit 418, Cambridge Science Park, Milton Road, Cambridge CB4 0PA, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ayscough
mesh_terms: D002491:Central Nervous System Agents; D055808:Drug Discovery
chemical_list: D002491:Central Nervous System Agents