Substituted 4-morpholine N-arylsulfonamides as γ-secretase inhibitors
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- 作者：Zhiqiang Zhaoa ; zhiqiang.zhao@merck.com" class="auth_mail" title="E-mail the corresponding author ; Dmitri A. Pissarnitskia ; Hubert B. Josiena ; Thomas A. Baraa ; John W. Cladera ; Hongmei Lia ; Mark D. McBriara ; Murali Rajagopalana ; Ruo Xua ; Giuseppe Terracinab ; Lynn Hydeb ; Lixin Songb ; Lili Zhangb ; Eric M. Parkerb ; Rebecca Ostermanc ; Alexei V. Buevichc
- 关键词：γ-secretase inhibitor ; Alzheimer's disease ; substituted 4-morpholine sulfonamide
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：29 November 2016
- 年：2016
- 卷：124
- 期：Complete
- 页码：36-48
- 全文大小：1589 K
文摘
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γ-Secretase inhibitors arrest formation of amyloid-β, which plays a role in Alzheimer's disease.
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Scissile carbamate bond of a known inhibitor was replaced with the non-scissile carbon
carbon bond.- •
The effect of introduction of polarity (oxygen atoms) in various parts of molecule has been studied.
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Stability and potency of the series was improved, while CYP3A4 inhibition was mitigated.