Author/Authors :
Jung-Hwan Park، نويسنده , , Jin Kyu Choi، نويسنده , , Eunjung Lee، نويسنده , , Jae Kyun Lee، نويسنده , , Hyewhon Rhim، نويسنده , , Seon Hee Seo، نويسنده , , Yoonjee Kim، نويسنده , , Munikumar Reddy Doddareddy، نويسنده , , Ae Nim Pae، نويسنده , , Jahyo Kang، نويسنده , , Eun Joo Roh، نويسنده ,
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 α1G and α1H 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 IC50 values than Mibefradil.
