Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers.
We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca(2+) channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca(2+) channels and N-type Ca(2+) channels. Among them, 5b (KYS05044, IC(50)=0.56+/-0.10 microM) was identified as potent T-type Ca(2+) channel blocker with in vitro selectivity profile at meaningful level (T/N-type, SI=>100).
Rhim
Hyewhon
H
Life Sciences Division, Korea Institute of Science & Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Lee
Yong Sup
YS
Park
Seong Jun
SJ
Chung
Bong Young
BY
Lee
Jae Yeol
JY
D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / 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; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D011799:Quinazolines