Synthesis and SAR studies of a novel series of T-type calcium channel blockers.
For the novel, potent, and selective T-type Ca2+ channel blockers, a series of sulfonamido-containing 3,4-dihydroquinazoline derivatives were prepared and evaluated for their blocking actions on T- and N-type Ca2+ channels. Among them, 9c (KYS05064, IC50 = 0.96 +/- 0.22 microM) was found to be as potent as Mibefradil and also showed the highest selectivity for T-type Ca2+ channel with no effect on N-type Ca2+ channel.
Park
Seong Jun
SJ
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Park
Sung Jun
SJ
Lee
Min Joo
MJ
Rhim
Hyewhon
H
Kim
Yoonjee
Y
Lee
Jung-Ha
JH
Chung
Bong Young
BY
Lee
Jae Yeol
JY
D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D007928:Lethal Dose 50; D020748:Mibefradil / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D011799:Quinazolines; D013449:Sulfonamides; D020748:Mibefradil