alpha,alpha-Cyclic aminoacids as useful scaffolds for the preparation of hNK(2) receptor antagonists

Alessandro Sisto; Maria Altamura; Franco Cardinali; Piero D'Andrea; Cristina Rossi; Daniela Fattori

doi:10.1016/j.bmcl.2007.06.053

alpha,alpha-Cyclic aminoacids as useful scaffolds for the preparation of hNK(2) receptor antagonists

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4841-4. doi: 10.1016/j.bmcl.2007.06.053. Epub 2007 Jun 20.

Authors

Alessandro Sisto¹, Maria Altamura, Franco Cardinali, Piero D'Andrea, Cristina Rossi, Daniela Fattori

Affiliation

¹ Menarini Ricerche SpA, via Tito Speri 10, 00040 Pomezia, Rome, Italy.

PMID: 17604625
DOI: 10.1016/j.bmcl.2007.06.053

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry*
Animals
Chemistry, Pharmaceutical / methods
Drug Design
Guinea Pigs
Humans
Hydrogen-Ion Concentration
Kinetics
Models, Chemical
Models, Molecular
Molecular Conformation
Peptides / chemistry
Phenylalanine / chemistry
Receptors, Neurokinin-2 / antagonists & inhibitors*
Solubility

Substances

Amino Acids
Peptides
Receptors, Neurokinin-2
Phenylalanine