Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors.
Screening of the Roche compound library led to the identification of the benzoylpiperazine 7 as a structurally novel GlyT1 inhibitor. The SAR which was developed in this series resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform, drug-like properties, and in vivo efficacy after oral administration.
Pinard
Emmanuel
E
F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. emmanuel.pinard@roche.com
Alberati
Daniela
D
Borroni
Edilio
E
Fischer
Holger
H
Hainzl
Dominik
D
Jolidon
Synèse
S
Moreau
Jean-Luc
JL
Narquizian
Robert
R
Nettekoven
Matthias
M
Norcross
Roger D
RD
Stalder
Henri
H
Thomas
Andrew W
AW