Generation of a new class of hNK2 receptor ligands using the ‘fragment approach’

The so called ‘fragment approach’ was applied in the search for new leads as selective hNK2 antagonists. A first round of structural space exploration through the use of bond rigidity as scaffold to support the fragments, afforded 27a as 200 nM hNK2 ligand. Further refinement gave MEN 14933 as a 16 nM hNK2 ligand, selective versus hNK1, of a novel class. Conformational analysis was used to study results and plan future work.