Discovery of N-{[1-(propylsulfonyl)-4-pyridin-2-ylpiperidin-4-yl]methyl}benzamides as novel, selective and potent GlyT1 inhibitors.
Employing an iterative analogue library approach, novel potent and selective glycine transporter 1 (GlyT1) inhibitors containing a 4-pyridin-2-ylpiperidine sulfonamide have been discovered. These inhibitors are devoid of time-dependent CYP inhibition activity and exhibit improved aqueous solubility versus the corresponding 4-phenylpiperidine analogues.
Zhao
Zhijian
Z
Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck & Co., Inc., WP-14-1, PO Box 4 Sumneytown Pike, West Point, PA 19486, USA.
Leister
William H
WH
O'Brien
Julie A
JA
Lemaire
Wei
W
Williams
David L
DL
Jacobson
Marlene A
MA
Sur
Cyrille
C
Kinney
Gene G
GG
Pettibone
Doug J
DJ
Tiller
Philip R
PR
Smith
Sheri
S
Hartman
George D
GD
Lindsley
Craig W
CW
Wolkenberg
Scott E
SE
D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D001549:Benzamides; D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; C493268:SLC6A9 protein, human; D013449:Sulfonamides