Lead discovery and optimization of T-type calcium channel blockers.

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Park JH, Choi JK, Lee E, Lee JK, Rhim H, Seo SH, Kim Y, Doddareddy MR, Pae AN, Kang J, Roh EJ

Lead discovery and optimization of T-type calcium channel blockers.

Bioorg Med Chem. 2007 Feb 1;15(3):1409-19. Epub 2006 Nov 10.

PubMed ID

17150365 [ View in PubMed

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Abstract

A series of compounds were designed as T-type calcium channel blocker containing 6 or 5 pharmacophore features from structure-based virtual screening. To optimize the suggested structure, over 130 derivatives were synthesized and their inhibitory activities on T-type calcium channel were assayed using in vitro screening system with alpha1(G) and alpha1(H) clones. For the compounds with higher activities in FDSS assay system, the efficacy was measured by patch-clamp method. Among the library with 5 features, alkaneamide derivatives (7b, 9j, 11b, 11g, 11h) with 4-arylsubstituted piperazine showed better IC(50) values than Mibefradil.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mibefradil	Voltage-dependent T-type calcium channel subunit alpha-1G	IC 50 (nM)	1340	N/A	N/A	Details