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Symmetric kv1.5 blockers discovered by focused screening.

ABSTRACT: Guided by computational methods, a set of 1920 compounds were selected from the AstraZeneca corporate collection and screened for Kv1.5 activity. To facilitate rapid generation of structure-activity relationships, special attention was given to selecting subsets of structurally similar molecules by using a maximum common substructure similarity-based procedure. The focused screen hit rate was relatively high (12%). More importantly, a structural series featured by the symmetric 1,2-diphenylethane-1,2-diamine substructure was identified as potent Kv.1.5 blockers. The property profile for the series is shown to meet stringent lead-optimization criteria, providing a springboard for the development of a new and safe treatment for atrial fibrillation.

SUBMITTER: Bostrom J

PROVIDER: S-EPMC4025650 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Symmetric kv1.5 blockers discovered by focused screening.

Boström Jonas J

ACS medicinal chemistry letters 20120816 9

Guided by computational methods, a set of 1920 compounds were selected from the AstraZeneca corporate collection and screened for Kv1.5 activity. To facilitate rapid generation of structure-activity relationships, special attention was given to selecting subsets of structurally similar molecules by using a maximum common substructure similarity-based procedure. The focused screen hit rate was relatively high (12%). More importantly, a structural series featured by the symmetric 1,2-diphenylethan ...[more]

PMID: 24900546

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