title: Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.
abstract: 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.
authors.affiliation: Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Jo
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Seo
authors.forename: Yoonji
authors.initials: Y
authors.lastname: Kim
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Seo
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Cha
authors.forename: Hun Yeong
authors.initials: HY
authors.lastname: Koh
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
mesh_terms: 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
chemical_list: D000577:Amides; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D011799:Quinazolines