Structure activity relationship studies of tricyclic bispyran sulfone ¦Ã-secretase inhibitors
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- 作者：Wen-Lian Wu ; wen-lian.wu@merck.com ; Theodros Asberom ; Thomas Bara ; Chad Bennett ; Duane A. Burnett ; John Clader ; Martin Domalski ; William J. Greenlee ; Hubert Josien ; Mark McBriar ; Murali Rajagopalan ; Monica Vicarel ; Ruo Xu ; Lynn A. Hyde ; Robert A. Del Vecchio ; Mary E. Cohen-Williams ; Lixin Song ; Julie Lee ; Giuseppe Terracina ; Qi Zhang ; Amin Nomeir ; Eric M. Parker ; Lili Zhang
- 关键词：Alzheimer&rsquo ; s disease ; ¦Ã-Secretase inhibitor ; Structure activity relationship ; Sulfone
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：1 February, 2013
- 年：2013
- 卷：23
- 期：3
- 页码：844-849
- 全文大小：965 K
文摘
An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (?)-1a (SCH 900229), a potent, PS1-selective ¦Ã-secretase inhibitor and clinical candidate for the treatment of Alzheimer¡¯s disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone analogs, (?)-1b and (?)-1c, are equipotent to compound (?)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.