Generation of a new class of hNK(2) receptor ligands using the 'fragment approach'.
The so called 'fragment approach' was applied in the search for new leads as selective hNK(2) 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 hNK(2) ligand. Further refinement gave MEN 14933 as a 16 nM hNK(2) ligand, selective versus hNK(1), of a novel class. Conformational analysis was used to study results and plan future work.
D'Andrea
Piero
P
Menarini Ricerche S.p.A., via Tito Speri 10, 00040 Pomezia, Rome, Italy.
Porcelloni
Marina
M
Madami
Andrea
A
Patacchini
Riccardo
R
Altamura
Maria
M
Fattori
Daniela
D
D000577:Amides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry
D000577:Amides; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D014508:Urea