Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.
T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pains. Since the withdrawal of mibefradil, a T-type calcium channel blocker, there have been a lot of efforts to develop T-type calcium channel blockers. A small molecule library of dioxoquinazoline carboxamide derivatives containing 155 compounds was designed, synthesized, and biologically evaluated for T-type calcium channel blocking activity. Among those compounds synthesized, the compound 1n shows the most potent T-type calcium current blocking activity with an IC(50) value of 1.52 microM, which is comparable to that of mibefradil.
Jo
Mi Na
MN
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Seo
Hee Jeong
HJ
Kim
Yoonji
Y
Seo
Seon Hee
SH
Rhim
Hyewhon
H
Cho
Yong Seo
YS
Cha
Joo Hwan
JH
Koh
Hun Yeong
HY
Choo
Hyunah
H
Pae
Ae Nim
AN
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D011799:Quinazolines