Ligand identification for G-protein-coupled receptors: a lead generation perspective.
This review addresses strategies for the generation of ligands for G-protein-coupled receptors outside classical high-throughput screening and literature based approaches. These range from the chemical intuition-based strategies of endogenous ligand elaboration and privileged structure decoration to the in silico approaches of virtual screening and de novo design. Examples are cited where supporting pharmacological data has been presented.
Bleicher
Konrad H
KH
F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Lead Generation, PRBD-CI, Bldg 65/410, CH-4070 Basel, Switzerland. konrad.bleicher@roche.com
Green
Luke G
LG
Martin
Rainer E
RE
Rogers-Evans
Mark
M
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D019295:Computational Biology; D016208:Databases, Factual; D015195:Drug Design; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry
D007093:Imidazoles; D008024:Ligands; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D018100:Receptors, Histamine H3; D013890:Thiourea; C086108:clobenpropit