Referenced in: none

Automatically associated channels: Kv11.1

Title: The design and synthesis of novel, potent and orally bioavailable N-aryl piperazine-1-carboxamide CCR2 antagonists with very high hERG selectivity.

Authors: John G Cumming, Justin F Bower, David Waterson, Alan Faull, Philip J Poyser, Paul Turner, Benjamin McDermott, Andrew D Campbell, Julian Hudson, Michael James, Jon Winter, Christine Wood

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Jun 15 , 22, 3895-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22608963

Abstract
A novel N-aryl piperazine-1-carboxamide series of human CCR2 chemokine receptor antagonists was discovered. Early analogues were potent at CCR2 but also inhibited the hERG cardiac ion channel. Structural modifications which decreased lipophilicity and basicity resulted in the identification of a sub-series with an improved margin over hERG. The pharmacological and pharmacokinetic properties of the lead compound from this series, N-(3,4-dichlorophenyl)-4-[(2R)-4-isopropylpiperazine-2-carbonyl]piperazine-1-carboxamide, are described.