Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides

Zhijian Zhao; Julie A O'Brien; Wei Lemaire; David L Williams Jr; Marlene A Jacobson; Cyrille Sur; Doug J Pettibone; Philip R Tiller; Sheri Smith; George D Hartman; Scott E Wolkenberg; Craig W Lindsley

doi:10.1016/j.bmcl.2006.08.131

Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine-4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides

Bioorg Med Chem Lett. 2006 Dec 1;16(23):5968-72. doi: 10.1016/j.bmcl.2006.08.131. Epub 2006 Sep 20.

Authors

Zhijian Zhao¹, Julie A O'Brien, Wei Lemaire, David L Williams Jr, Marlene A Jacobson, Cyrille Sur, Doug J Pettibone, Philip R Tiller, Sheri Smith, George D Hartman, Scott E Wolkenberg, Craig W Lindsley

Affiliation

¹ Department of Medicinal Chemistry, Merck and Co., Inc., PO Box 4, West Point, PA 19486, USA. [email protected] <[email protected]>

PMID: 16987662
DOI: 10.1016/j.bmcl.2006.08.131

Abstract

This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of potent and selective non-sarcosine-derived GlyT1 inhibitors.

MeSH terms

Amides / chemistry
Animals
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology*
Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Glycine Plasma Membrane Transport Proteins / metabolism
Humans
Methylation
Mice
Molecular Structure
Morpholines / chemistry*
Piperidines / chemistry*
Rats
Structure-Activity Relationship

Substances

Amides
Benzamides
Glycine Plasma Membrane Transport Proteins
Morpholines
Piperidines
piperidine