alpha,alpha-Cyclic aminoacids as useful scaffolds for the preparation of hNK(2) receptor antagonists.
MEN 15596 is a small molecule, potent and selective antagonist of NK(2) receptor, possessing high affinity and potency at the guinea-pig and human receptors whose pharmacological characterization has been recently published. Here we report how the corresponding class of compounds was derived from a tri-peptide library and the first optimization round to improve both in vitro activity and physicochemical properties.
Sisto
Alessandro
A
Menarini Ricerche SpA, via Tito Speri 10, 00040 Pomezia, Rome, Italy.
Altamura
Maria
M
Cardinali
Franco
F
D'Andrea
Piero
P
Rossi
Cristina
C
Fattori
Daniela
D
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D012995:Solubility
D000596:Amino Acids; D010455:Peptides; D018041:Receptors, Neurokinin-2; D010649:Phenylalanine