Optimisation of a series of potent, selective and orally bioavailable GlyT1 inhibitors.
A series of heterocyclic sulfonamides have been developed which are potent and selective inhibitors of hGlyT1. SAR studies to optimise the in vitro and in vivo properties are described. Optimisation of the central scaffold resulted in cyclohexane sulfones 28 and 29, which have good PK properties and show promise for further development.
Thomson
Joanne L
JL
Department of Medicinal Chemistry, Merck Sharp and Dohme, Neuroscience Research Centre, Harlow, Essex, UK.
Blackaby
Wesley P
WP
Jennings
Andrew S R
AS
Goodacre
Simon C
SC
Pike
Andrew
A
Thomas
Steve
S
Brown
Terry A
TA
Smith
Alison
A
Pillai
Gopalan
G
Street
Leslie J
LJ
Lewis
Richard T
RT