Synthesis and biological evaluation of novel T-type Ca2+ channel blockers.
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.
Jung
Hee Kyung
HK
Lifescience Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Doddareddy
Munikumar Reddy
MR
Cha
Joo Hwan
JH
Rhim
Hyewhon
H
Cho
Yong Seo
YS
Koh
Hun Yeong
HY
Jung
Bong Young
BY
Pae
Ae Nim
AN
D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D007555:Isoxazoles; D008024:Ligands; D010879:Piperazines; D002118:Calcium