Title: Mitigating hERG inhibition: design of orally bioavailable CCR5 antagonists as potent inhibitors of R5 HIV-1 replication
Authors: Skerlj, Renato ×
Bridger, Gary
Zhou, Yuanxi
Bourque, Elyse
McEachern, Ernest
Danthi, Sanjay
Langille, Jonathan
Harwig, Curtis
Veale, Duane
Carpenter, Bryon
Bey, Michael
Baird, Ian
Wilson, Trevor
Metz, Markus
MacFarland, Ron
Mosi, Renee
Bodart, Veronique
Wong, Rebecca
Fricker, Simon
Huskens, Dana
Schols, Dominique #
Issue Date: Mar-2012
Publisher: Amer chemical soc
Series Title: ACS Medicinal Chemistry Letters vol:3 issue:3 pages:216-221
Abstract: A series of CCR5 antagonists representing the thiophene-3-yl-methyl ureas were designed that met the pharmacological criteria for HIV-1 inhibition and mitigated a human ether-a-go-go related gene (hERG) inhibition liability. Reducing lipophilicity was the main design criteria used to identify compounds that did not inhibit the hERG channel, but subtle structural modifications were also important. Interestingly, within this series, compounds with low hERG inhibition prolonged the action potential duration (APD) in dog Purkinje fibers, suggesting a mixed effect on cardiac ion channels.
ISSN: 1948-5875
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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