title: Dual structure-activity relationship of osteoclastogenesis inhibitor methyl gerfelin based on TEG scanning.
abstract: Methyl gerfelin derivatives, each having an amine-terminated tri(ethylene glycol) linker at the peripheral position, were designed and systematically synthesized. These "TEGylated" derivatives were then subjected to a structure-activity relationship (SAR) study to examine their glyoxalase 1-inhibition activity and binding affinity toward the three binding proteins identified. Among the derivatives synthesized, that with a NH(2)-TEG linker at the C6-methyl group showed the most potent glyoxalase 1-inhibiting activity and glyoxalase 1 selectivity. These results indicated that derivatization at the C6-methyl group would be suitable for the further development of selective glyoxalase 1 inhibitors.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. nkanoh@m.tohoku.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanoh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawatani
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katou
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Iwabuchi
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004987:Ethers / Q000737:chemistry* / Q000494:pharmacology*; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008745:Methylation; D051379:Mice; D010010:Osteoclasts / Q000166:cytology*; D013329:Structure-Activity Relationship
chemical_list: C477902:4-carboxy-5,5'-dihydroxy-3,3'-dimethyl-diphenylether; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D004987:Ethers; D007791:Lactoylglutathione Lyase