Synthesis and Biological Evaluation of 3-Biphenyl-4-yl-4-phenyl-4H-1,2,4-triazoles as Novel Glycine Transporter 1 Inhibitors

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• 作者：Takashi Sugane ; Takahiko Tobe ; Wataru Hamaguchi ; Itsuro Shimada ; Kyoichi Maeno ; Junji Miyata ; Takeshi Suzuki ; Tetsuya Kimizuka ; Atsuyuki Kohara ; Takuma Morita ; Hitoshi Doihara ; Kyouko Saita ; Masaki Aota ; Masako Furutani ; Yoshiaki Shimada ; Noritaka Hamada ; Shuichi Sakamoto ; Shin-ichi Tsukamoto
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 13, 2011
• 年：2011
• 卷：54
• 期：1
• 页码：387-391
• 全文大小：776K
• 年卷期：v.54,no.1(January 13, 2011)
• ISSN：1520-4804

文摘

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.