Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as 纬-secretase modulators

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• 作者：Takafumi Takai ; ^{takafumi.takai@takeda.com" class="auth_mail" title="E-mail the corresponding author} ; Yasutaka Hoashi ; Yoshihide Tomata ; Sachie Morimoto ; Minoru Nakamura ; Tomomichi Watanabe ; Tomoko Igari ; Tatsuki Koike
• 关键词：AFBKWRWMZOOOIR-QGZVFWFLSA-N
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：1 October 2015
• 年：2015
• 卷：25
• 期：19
• 页码：4245-4249
• 全文大小：1092 K

文摘

Novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives were designed, synthesized, and evaluated as 纬-secretase modulators (GSMs). An optimization study of this series resulted in the identification of (R)-11j, which showed a potent A尾₄₂-lowering effect, high bioavailability and good blood–brain barrier permeability in mice. Oral administration of (R)-11j significantly reduced brain A尾₄₂ in mice at a dose of 10 mg/kg.