Adenosine analogue inhibitors of S-adenosylhomocysteine hydrolase

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• 作者：Antonella Converso^a ; ^{antonella_converso@merck.com" class="auth_mail} ; Timothy Hartingh^a ; Mark E. Fraley^a ; Robert M. Garbaccio^a ; George D. Hartman^a ; Shaei Y. Huang^a ; John M. Majercak^b ; Alexander McCampbell^c ; Sang Jin Na^b ; William J. Ray^c ; Mary J. Savage^c ; Carrie Wolffe^b ; Suzie Yeh^d ; Yuanjiang Yu^b ; Rebecca White^d ; Rena Zhang^d
• 关键词：Adenosine analogues ; AHCY ; Alzheimer&rsquo ; s disease ; Homocysteine ; SAH
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 June 2014
• 年：2014
• 卷：24
• 期：12
• 页码：2737-2740
• 全文大小：2310 K

文摘

Elevated plasma homocysteine (Hcy) levels are an independent risk factor for the onset and progression of Alzheimer’s disease. Reduction of Hcy to normal levels therefore presents a new approach for disease modification. Hcy is produced by the cytosolic enzyme S-adenosylhomocysteine hydrolase (AHCY), which converts S-adenosylhomocysteine (SAH) to Hcy and adenosine. Herein we describe the design and characterization of novel, substrate-based S-adenosylhomocysteine hydrolase inhibitors with low nanomolar potency in vitro and robust activity in vivo.