Utility of NMR in lead optimization: fragment-based approaches.
NMR has proven to be a valuable tool for identifying small molecule drug leads that serve as starting points for lead optimization programs. In addition, NMR screening can also be applied during lead optimization in order to improve the pharmacokinetic properties of a compound. In this paper we review the NMR methods that can be used for this purpose. Several examples are then summarized to demonstrate the usefulness of fragment-based approaches in optimizing the physical properties of potential drug candidates.
Huth
Jeffrey R
JR
Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. jeff.huth@abbott.com
Sun
Chaohong
C
D000818:Animals; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D017076:Computer-Aided Design; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010599:Pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
D008024:Ligands