Synthesis and pharmacological characterization of constrained analogues of Vestipitant as in vitro potent and orally active NK(1) receptor antagonists.
A focused exploration targeting conformationally restricted analogues of Vestipitant, resulted in the discovery of novel, in vitro potent NK(1) antagonists. In particular, two of the compounds reported exhibited a good pharmacokinetic (PK) profile and produced anxiolytic-like effects in the gerbil foot tapping (GFT) in vivo model.
Sabbatini
Fabio M
FM
Neurosciences Centre of Excellence for Drug Discovery and Molecular Discovery Research, GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, 37135 Verona, Italy. Fabio.M.Sabbatini@GSK.com
Di Fabio
Romano
R
Griffante
Cristiana
C
Pentassuglia
Giorgio
G
Zonzini
Laura
L
Melotto
Sergio
S
Alvaro
Giuseppe
G
Capelli
Anna M
AM
Pippo
Lara
L
Perdona'
Elisabetta
E
St Denis
Yves
Y
Costa
Silvano
S
Corsi
Mauro
M
D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015195:Drug Design; D005464:Fluorobenzenes; D006801:Humans; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D018040:Receptors, Neurokinin-1 / Q000378:metabolism
D014151:Anti-Anxiety Agents; D005464:Fluorobenzenes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C534550:vestipitant