title: Synthesis and biological evaluation of novel T-type Ca2+ channel blockers.
abstract: A small molecule library of piperazinylalkylisoxazole derivatives containing about 600 compounds was designed, synthesized and evaluated for blocking effects on T-type Ca(2+) channel. Several ligands were identified to possess high inhibitory activity against the T-type Ca(2+) channel. The compound 21 with trifluoromethyl substituents at C(3)-position of phenyl group (R(1)) and C(2)-position of phenyl group (R(2)) showed the highest inhibitory activity with IC(50) value of 1.02 microM, which is comparable to that of mibefradil.
authors.affiliation: Lifescience Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jung
authors.forename: Munikumar Reddy
authors.initials: MR
authors.lastname: Doddareddy
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Cha
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
authors.forename: Hun Yeong
authors.initials: HY
authors.lastname: Koh
authors.forename: Bong Young
authors.initials: BY
authors.lastname: Jung
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D007555:Isoxazoles; D008024:Ligands; D010879:Piperazines; D002118:Calcium