title: Silicon switch approach in TRPV1 antagonist MK-056 and its analogues.
abstract: In searching for opportunities to exploit the benefits of silicon in TRPV1 research, we tried to investigate the pharmacological effects of sila-substitution (C/Si exchange) of tert-butyl group in the MK-056 series. Compound 13a, with a 4-positioned trimethylsilanyl group on the B ring in place of tert-butyl group, exhibited the most potent antagonist activity with IC(50) values of 0.15 microM, which is almost equipotent with that of MK-056. This is the first example that tert-butyl group on MK-056 series can be replaced to the other substituent without loss of activity.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Yongsan-gu, Seoul 140-742, Republic of Korea.
authors.forename: Minsun
authors.initials: M
authors.lastname: Chang
authors.forename: Seol-Rin
authors.initials: SR
authors.lastname: Park
authors.forename: Juhyun
authors.initials: J
authors.lastname: Kim
authors.forename: Mijung
authors.initials: M
authors.lastname: Jang
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Hyeung-Geun
authors.initials: HG
authors.lastname: Park
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
authors.forename: Yeon Su
authors.initials: YS
authors.lastname: Jeong
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Hee-Doo
authors.initials: HD
authors.lastname: Kim
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000737:chemistry*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D010670:Phenylthiourea; C037877:benzylthiourea; D002118:Calcium; D012825:Silicon