1,3-diaminopropan-2-ol sulfonamides as potent and selective inhibitors of the glycine transporter type 1

Shahzad S Rahman; Steven Coulton; Hugh J Herdon; Graham F Joiner; Jian Jin; Roderick A Porter

doi:10.1016/j.bmcl.2006.12.063

1,3-diaminopropan-2-ol sulfonamides as potent and selective inhibitors of the glycine transporter type 1

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1741-5. doi: 10.1016/j.bmcl.2006.12.063. Epub 2006 Dec 22.

Authors

Shahzad S Rahman¹, Steven Coulton, Hugh J Herdon, Graham F Joiner, Jian Jin, Roderick A Porter

Affiliation

¹ Discovery Medicinal Chemistry, GlaxoSmithKline, Harlow, Essex CM19 5AW, UK. [email protected]

PMID: 17234406
DOI: 10.1016/j.bmcl.2006.12.063

Abstract

High throughput screening led to the discovery of a novel series of 1,3-diaminopropan-2-ol sulfonamides as selective GlyT-1 inhibitors. Structure-activity relationships of this novel series and optimisation of the initial hit that led to the identification of (2), a potent and selective GlyT-1 inhibitor, are also presented.

MeSH terms

Animals
Cell Line, Tumor
Chromatography, High Pressure Liquid
Computer Simulation
Drug Evaluation, Preclinical
Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Humans
Isomerism
Molecular Conformation
Rats
Spectrophotometry, Ultraviolet
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology*

Substances

Glycine Plasma Membrane Transport Proteins
Sulfonamides