@article{5efb2c9608204e5e88933276a7046a6e,
title = "Structure–activity relationship studies in a new series of 2-amino-N-phenylacetamide inhibitors of Slack potassium channels",
abstract = "In this Letter we describe structure–activity relationship (SAR) studies conducted in five distinct regions of a new 2-amino-N-phenylacetamides series of Slack potassium channel inhibitors exemplified by recently disclosed high-throughput screening (HTS) hit VU0606170 (4). New analogs were screened in a thallium (Tl+) flux assay in HEK-293 cells stably expressing wild-type human (WT) Slack. Selected analogs were screened in Tl+ flux versus A934T Slack and other Slo family members Slick and Maxi-K and evaluated in whole-cell electrophysiology (EP) assays using an automated patch clamp system. Results revealed the series to have flat SAR with significant structural modifications resulting in a loss of Slack activity. More minor changes led to compounds with Slack activity and Slo family selectivity similar to the HTS hit.",
keywords = "2-Amino-N-phenylacetamide, EIMFS, K1.1, KCNT1, MMPSI, Slack, Slo2.2",
author = "Qunies, {Alshaima'a M.} and Mishra, {Nigam M.} and Spitznagel, {Brittany D.} and Yu Du and Acu{\~n}a, {Valerie S.} and {David Weaver}, C. and Emmitte, {Kyle A.}",
note = "Funding Information: We thank the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA (R33NS109521 to C.D.W. and K.A.E.) for their support of our program in the development of small molecule inhibitors of Slack channels. Funding for the WaveFront Biosciences Panoptic kinetic imaging plate reader and the Syncropatch 768 PE platform was provided by the Office of The Director (OD) of the National Institutes of Health under the award numbers 1S10OD021734 and 1S10OD021734, respectively. Funding Information: We thank the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA ( R33NS109521 to C.D.W. and K.A.E.) for their support of our program in the development of small molecule inhibitors of Slack channels. Funding for the WaveFront Biosciences Panoptic kinetic imaging plate reader and the Syncropatch 768 PE platform was provided by the Office of The Director (OD) of the National Institutes of Health under the award numbers 1S10OD021734 and 1S10OD021734, respectively. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2022",
month = nov,
day = "15",
doi = "10.1016/j.bmcl.2022.129013",
language = "English",
volume = "76",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Ltd",
}