Examples will be presented where NMR-deived 3d-structures of drug candidates assisted drug discovery efforts. In the FVIIa program enhanced potency was achieved by the synthesis of macrocyclic compounds albeit at the emergence of conformational heterogeneity. NMR 3d structures and kinetic studies in concert with molecular modeling and medicinal chemistry efforts led to the design of improved potency inhibitors which adoptd the bioactive conformers in solution. In addition, examples will be presented where cyclic retraints may induce bio-active conformers in peptides. The emphasis will focus on discussing the methods used in generating 3d-structures using NMR-data.
