Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and Efficacious γ-Secretase Inhibitors

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• 作者：Xiaocong M. Ye ; Andrei W. Konradi ; Jenifer Smith ; Ying-Zi Xu ; Darren Dressen ; Albert W. Garofalo ; Jennifer Marugg ; Hing L. Sham ; Anh P. Truong ; Jacek Jagodzinski ; Michael Pleiss ; Hongbin Zhang ; Erich
• 关键词：Alzheimer’ ; s disease ; Amyloid precursor protein ; γ ; -Secretase ; γ ; -Secretase inhibitor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 April 2010
• 年：2010
• 卷：20
• 期：7
• 页码：2195-2199
• 全文大小：742 K

文摘

Discovery of a series of pyrazolopiperidine sulfonamide based γ-secretase inhibitors and its SAR evolution is described. Significant increases in APP potency on the pyrazolopiperidine scaffold over the original N-bicyclic sulfonamide scaffold were achieved and this potency increase translated in an improved in vivo efficacy.