title: Heterocycle-linked phenylbenzyl amides as novel TRPV1 antagonists and their TRPV1 binding modes: constraint-induced enhancement of in vitro and in vivo activities.
abstract: A series of heterocycle-linked constrained phenylbenzyl amides were found to be TRPV1 antagonists with promising in vivo profiles. In particular, one of the analogues containing a furan linker exhibited excellent TRPV1 antagonistic activity and in vivo analgesic efficacy. In addition, the binding modes of dibenzyl thiourea, benzylphenethyl amide, and furan-linked phenylbenzyl amide were examined by using the flexible docking study within the rTRPV1 homology model.
authors.affiliation: College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Nam-Jung
authors.initials: NJ
authors.lastname: Kim
authors.forename: Fu-Nan
authors.initials: FN
authors.lastname: Li
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Seul-gi
authors.initials: SG
authors.lastname: Park
authors.forename: Kyeojin
authors.initials: K
authors.lastname: Kim
authors.forename: Changjin
authors.initials: C
authors.lastname: Lim
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Han
authors.forename: Hwayoung
authors.initials: H
authors.lastname: Yun
authors.forename: Jong-Wha
authors.initials: JW
authors.lastname: Jung
authors.forename: Hyeung-geun
authors.initials: HG
authors.lastname: Park
authors.forename: Hee-Doo
authors.initials: HD
authors.lastname: Kim
authors.forename: Byoung Young
authors.initials: BY
authors.lastname: Woo
authors.forename: Song Seok
authors.initials: SS
authors.lastname: Shin
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Jeong
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Park
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000700:Analgesics / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001665:Binding Sites; D005663:Furans / Q000737:chemistry; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013890:Thiourea / Q000737:chemistry
chemical_list: D000577:Amides; D000700:Analgesics; D005663:Furans; D006571:Heterocyclic Compounds; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; D013890:Thiourea; C039281:furan