title: Synthesis and biological evaluation of 3-biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as novel glycine transporter 1 inhibitors.
abstract: We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revealed that 6p had excellent oral bioavailability and ameliorated learning impairment in passive avoidance tasks in mice.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan. takashi.sugane@jp.astellas.com
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugane
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tobe
authors.forename: Wataru
authors.initials: W
authors.lastname: Hamaguchi
authors.forename: Itsuro
authors.initials: I
authors.lastname: Shimada
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Maeno
authors.forename: Junji
authors.initials: J
authors.lastname: Miyata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimizuka
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Kohara
authors.forename: Takuma
authors.initials: T
authors.lastname: Morita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Doihara
authors.forename: Kyouko
authors.initials: K
authors.lastname: Saita
authors.forename: Masaki
authors.initials: M
authors.lastname: Aota
authors.forename: Masako
authors.initials: M
authors.lastname: Furutani
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shimada
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hamada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002463:Cell Membrane Permeability; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C562249:3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole; D001713:Biphenyl Compounds; D050487:Glycine Plasma Membrane Transport Proteins; D018697:Nootropic Agents; D014230:Triazoles