title: Synthesis and biological evaluation of novel T-type calcium channel blockers.
abstract: 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).
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, Republic of Korea.
authors.forename: Ja Youn
authors.initials: JY
authors.lastname: Choi
authors.forename: Han Na
authors.initials: HN
authors.lastname: Seo
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Lee
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Jeon
authors.forename: Joo Hi
authors.initials: JH
authors.lastname: Kang
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D007202:Indicators and Reagents; D011759:Pyrrolidines; D011799:Quinazolines; D020748:Mibefradil