Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides.
This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of potent and selective non-sarcosine-derived GlyT1 inhibitors.
Zhao
Zhijian
Z
Department of Medicinal Chemistry, Merck and Co., Inc., PO Box 4, West Point, PA 19486, USA. zhijian_zhao@merck.com <zhijian_zhao@merck.com>
O'Brien
Julie A
JA
Lemaire
Wei
W
Williams
David L
DL
Jacobson
Marlene A
MA
Sur
Cyrille
C
Pettibone
Doug J
DJ
Tiller
Philip R
PR
Smith
Sheri
S
Hartman
George D
GD
Wolkenberg
Scott E
SE
Lindsley
Craig W
CW
D000577:Amides / Q000737:chemistry; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides; D001549:Benzamides; D050487:Glycine Plasma Membrane Transport Proteins; D009025:Morpholines; D010880:Piperidines; C032727:piperidine