Synthesis and biological evaluation of novel T-type calcium channel blockers.
3,4-Dihydroquinazoline analogues substituted by N-methyl-N-(5-pyrrolidinopentyl)amine at the 2-position were synthesized and their blocking effects were evaluated for T- and N-type calcium channels. Compound 11b (KYS05080), compared to mibefradil (IC50=1.34+/-0.49 microM), was about 5-fold potent (IC50=0.26+/-0.01 microM) for T-type calcium channel (alpha1G) blocking and its selectivity of T/N-type was also improved (7.5 versus 1.4 of mibefradil).
Choi
Ja Youn
JY
Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, Republic of Korea.
Seo
Han Na
HN
Lee
Min Joo
MJ
Park
Seong Jun
SJ
Park
Sung Jun
SJ
Jeon
Ji Young
JY
Kang
Joo Hi
JH
Pae
Ae Nim
AN
Rhim
Hyewhon
H
Lee
Jae Yeol
JY
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D020748:Mibefradil / Q000494:pharmacology; D008958:Models, Molecular; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014981:Xenopus
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D007202:Indicators and Reagents; D011759:Pyrrolidines; D011799:Quinazolines; D020748:Mibefradil