ABSTRACT
Early phase drug discovery is a multi-parameter optimisation process. Finding drugable targets, discovering starting points for lead optimisation and creating novel structures with new biological properties within these constraints is challenging. As an example of a drug optimisation strategy, recent work on 5-HT1B antagonists will be described. This is put in the context of the drugability of the target, the desired physicochemical properties of the desired molecules and approaches to compound design to create high affinity, selective molecules that are optimised to have low Central Nervous System (CNS) penetration.
Subject(s)
Receptors, G-Protein-Coupled/metabolism , Serotonin 5-HT1 Receptor Antagonists/pharmacology , Serotonin 5-HT1 Receptor Antagonists/therapeutic use , Animals , Central Nervous System/drug effects , Central Nervous System/metabolism , Drug Design , Drug Discovery/methods , Humans , Ligands , Structure-Activity RelationshipABSTRACT
Computers have changed the way we do science. Surrounded by a sea of data and with phenomenal computing capacity, the methodology and approach to scientific problems is evolving into a partnership between experiment, theory and data analysis. Given the pace of change of the last twenty-five years, it seems folly to speculate on the future, but along with unpredictable leaps of progress there will be a continuous evolution of capability, which points to opportunities and improvements that will certainly appear as our discipline matures.
