Referenced in: none

Automatically associated channels: Kv11.1

Title: A novel, non-substrate-based series of glycine type 1 transporter inhibitors derived from high-throughput screening.

Authors: J Lowe, S Drozda, W Qian, M-C Peakman, J Liu, J Gibbs, J Harms, C Schmidt, K Fisher, C Strick, A Schmidt, M Vanase, L Lebel

Journal, date & volume: Bioorg. Med. Chem. Lett., 2007 Mar 15 , 17, 1675-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17257843

Abstract
The synthesis and structure-activity relationships (SAR) of a series of indane and tetralin inhibitors of the type 1 glycine transporter, derived from a high-throughput screening (HTS) hit, are described. Key modifications that reduced the 5HT1B receptor affinity of the HTS hit and the P450 2D6 inhibition of subsequent analogues are delineated. While these modifications led to potent and selective GlyT1 inhibitors, HERG affinity and human microsomal clearance remain an issue for this series of compounds.