Synthesis and biological evaluation of novel T-type Ca2+ channel blockers.
Bioorganic & medicinal chemistry 2004 Aug 1; 12(15):3965-70
Jung H HK, Doddareddy M MR, Cha J JH, Rhim H H, Cho Y YS, Koh H HY, Jung B BY, Pae A AN
Lifescience Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
A small molecule library of piperazinylalkylisoxazole derivatives containing about 600 compounds was designed, synthesized and evaluated for blocking effects on T-type Ca(2+) channel. Several ligands were identified to possess high inhibitory activity against the T-type Ca(2+) channel. The compound 21 with trifluoromethyl substituents at C(3)-position of phenyl group (R(1)) and C(2)-position of phenyl group (R(2)) showed the highest inhibitory activity with IC(50) value of 1.02 microM, which is comparable to that of mibefradil.

