Initial Optimization of a New Series of 纬-Secretase Modulators Derived from a Triterpene Glycoside
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- 作者：Nathan O. Fuller ; Jed L. Hubbs ; Wesley F. Austin ; Steffen P. Creaser ; Timothy D. McKee ; Robyn M. B. Loureiro ; Barbara Tate ; Weiming Xia ; Jeffrey L. Ives ; Mark A. Findeis ; Brian S. Bronk
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：November 8, 2012
- 年：2012
- 卷：3
- 期：11
- 页码：908-913
- 全文大小：367K
- 年卷期：v.3,no.11(November 8, 2012)
- ISSN：1948-5875
文摘
The discovery of a new series of 纬-secretase modulators is disclosed. Starting from a triterpene glycoside 纬-secretase modulator that gave a very low brain-to-plasma ratio, initial SAR and optimization involved replacement of a pendant sugar with a series of morpholines. This modification led to two compounds with significantly improved central nervous system (CNS) exposure.