title: Synthesis and structural optimization of multiple H-bonding region of diarylalkyl (thio)amides as novel TRPV1 antagonists.
abstract: Structural optimization of multiple H-bonding region and structure-activity relationship of diarylalkyl amides/thioamides as novel TRPV1 antagonists are described. In particular, we identified amide 34o and thioamides 35o and 35r, of which antagonistic activities were highly enhanced by an incorporation of cyano or vinyl-substituent to the multiple H-bonding region. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron with IC(50)s of 25, 32 and 28 nM, respectively.
authors.affiliation: College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Fu-Nan
authors.initials: FN
authors.lastname: Li
authors.forename: Nam-Jung
authors.initials: NJ
authors.lastname: Kim
authors.forename: Dong-Jo
authors.initials: DJ
authors.lastname: Chang
authors.forename: Jaebong
authors.initials: J
authors.lastname: Jang
authors.forename: Hannah
authors.initials: H
authors.lastname: Jang
authors.forename: Jong-Wha
authors.initials: JW
authors.lastname: Jung
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Jeong
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Hee-Doo
authors.initials: HD
authors.lastname: Kim
authors.forename: Hyeung-Geun
authors.initials: HG
authors.lastname: Park
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
mesh_terms: D000577:Amides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D050916:TRPV Cation Channels; D002118:Calcium