Small conformationally restricted piperidine N-arylsulfonamides as orally active γ-secretase inhibitors
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- 作者：Hubert Josien ; Thomas Bara ; Murali Rajagopalan ; Theodros Asberom ; John W. Clader ; Leonard Favreau ; William J. Greenlee ; Lynn A. Hyde ; Amin A. Nomeir ; Eric M. Parker ; Dmitri A. Pissarnitski ; Lixin Song
- 关键词：Alzheimer’ ; s disease ; γ ; -Secretase ; Inhibitor ; CYP 3A4 ; Sulfonamide ; Piperidine ; Conformational constraint
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：1 October 2007
- 年：2007
- 卷：17
- 期：19
- 页码：5330-5335
- 全文大小：208 K
文摘
The design and development of a new class of small 2,6-disubstituted piperidine N-arylsulfonamide γ-secretase inhibitors is reported. Lowering molecular weight including the use of conformational constraint led to compounds with less CYP 3A4 liability compared to early leads. Compounds active orally in lowering Aβ levels in Tg CRND8 mice were identified as potential treatments for Alzheimer’s disease.