Structure-activity relationship studies in a new series of 2-amino-N-phenylacetamide inhibitors of Slack potassium channels.
Bioorg Med Chem Lett
; 76: 129013, 2022 11 15.
Article
em En
| MEDLINE
| ID: mdl-36184030
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tálio
/
Canais de Potássio
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article