title: Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers.
abstract: To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against α(1G) calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 μM=61.85-71.99, hERG channel IC(50)=1.57 ± 0.14-4.98 ± 0.36 μM). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia.
authors.affiliation: Life/Health Division, Korea Institute of Science and Technology, 5 Wolsong-gil, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Woo
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Roh
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Seo
authors.forename: Chi Man
authors.initials: CM
authors.lastname: Song
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Kye Jung
authors.initials: KJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D020128:Inhibitory Concentration 50; D008024:Ligands; D020748:Mibefradil / Q000378:metabolism; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013127:Spinal Nerves / Q000601:surgery; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D008024:Ligands; D010880:Piperidines; D020748:Mibefradil