title: Generation of a new class of hNK(2) receptor ligands using the 'fragment approach'.
abstract: 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.
authors.affiliation: Menarini Ricerche S.p.A., via Tito Speri 10, 00040 Pomezia, Rome, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: D'Andrea
authors.forename: Marina
authors.initials: M
authors.lastname: Porcelloni
authors.forename: Andrea
authors.initials: A
authors.lastname: Madami
authors.forename: Riccardo
authors.initials: R
authors.lastname: Patacchini
authors.forename: Maria
authors.initials: M
authors.lastname: Altamura
authors.forename: Daniela
authors.initials: D
authors.lastname: Fattori
mesh_terms: 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
chemical_list: D000577:Amides; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D014508:Urea