Novel orally active morpholine N
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- 作者：Hubert Josien ; Thomas Bara ; Murali Rajagopalan ; John W. Clader ; William J. Greenlee ; Leonard Favreau ; Lynn A. Hyde ; Amin A. Nomeir ; Eric M. Parker ; Lixin Song ; Lili Zhang ; Qi Zhang
- 关键词：Alzheimer’ ; s disease ; γ ; -Secretase ; Inhibitor ; CYP 3A4 ; Sulfonamide ; Morpholine
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：1 November 2009
- 年：2009
- 卷：19
- 期：21
- 页码：6032-6037
- 全文大小：1248 K
文摘
A new class of 2,6-disubstituted morpholine N-arylsulfonamide γ-secretase inhibitors was designed based on the introduction of a morpholine core in lieu or piperidine in our lead series. This resulted in compounds with improved CYP 3A4 profiles. Several analogs that were active at lowering Aβ levels in Tg CRND8 mice upon oral administration were identified.