Repository logo
 

Multiple-parameter Optimization in Drug Discovery: Example of the 5-HT1B GPCR.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Glen, Robert Charles 
Galloway, Warren RJD 
Spring, David R 
Liwiki, Gemma 

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.

Description

Keywords

5-HT1B, Computer-Aided Molecular Design, PAH, Pulmonary Arterial Hypertension, Animals, Central Nervous System, Drug Design, Drug Discovery, Humans, Ligands, Receptors, G-Protein-Coupled, Serotonin 5-HT1 Receptor Antagonists, Structure-Activity Relationship

Journal Title

Mol Inform

Conference Name

Journal ISSN

1868-1743
1868-1751

Volume Title

Publisher

Wiley
Sponsorship
Royal Society (WM150022)
European Research Council (279337)
Engineering and Physical Sciences Research Council (EP/J016012/1)
Engineering and Physical Sciences Research Council (EP/K039520/1)
Biotechnology and Biological Sciences Research Council, Medical Research Council