title: Multiple-parameter Optimization in Drug Discovery: Example of the 5-HT1B GPCR.
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.
authors.affiliation: University of Cambridge, Cambridge, Cambridgeshire UNITED KINGDOM.
authors.forename: Robert Charles
authors.initials: RC
authors.lastname: Glen
authors.affiliation: University of Cambridge, Cambridge, Cambridgeshire UNITED KINGDOM.
authors.forename: Warren R J D
authors.initials: WR
authors.lastname: Galloway
authors.affiliation: University of Cambridge, Cambridge, Cambridgeshire UNITED KINGDOM.
authors.forename: David R
authors.initials: DR
authors.lastname: Spring
authors.affiliation: University of Cambridge, Cambridge, Cambridgeshire UNITED KINGDOM.
authors.forename: Gemma
authors.initials: G
authors.lastname: Liwiki
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D058829:Serotonin 5-HT1 Receptor Antagonists
keywords: 5-HT1B; Computer-Aided Molecular Design; PAH; Pulmonary Arterial Hypertension