title: Synthesis and evaluation of alpha,alpha'-disubstituted phenylacetate derivatives for T-type calcium channel blockers.
abstract: We have synthesized and evaluated alpha,alpha'-disubstituted phenylacetate derivatives that were designed as T-type calcium channel blockers. Among them, compound 10e (IC(50)=8.17+/-0.48nM) showed the most potent T-type calcium current blocking activity and higher potency than Mibefradil (IC(50)=1.34+/-0.49microM). The PK profile and subtype selectivity over L-type calcium channel were satisfied for further animal assay using disease model.
authors.affiliation: Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongyang, Seoul 130-650, Republic of Korea.
authors.forename: Hyung Kook
authors.initials: HK
authors.lastname: Lee
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Roh
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D020650:Combinatorial Chemistry Techniques; D004195:Disease Models, Animal; D015195:Drug Design; D020748:Mibefradil / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010648:Phenylacetates; D010879:Piperazines; D020748:Mibefradil