Structure-Activity Relationships of Strychnine Analogs at Glycine Receptors

被引：6
|
作者：
Mohsen, Amal M. Y. [1 ]
Heller, Eberhard [2 ]
Holzgrabe, Ulrike [2 ]
Jensen, Anders A. [3 ]
Zlotos, Darius P. [1 ]
机构：
[1] German Univ Cairo, Dept Pharmaceut Chem, Cairo 11835, Egypt
[2] Univ Wurzburg, Inst Pharm & Food Chem, DE-97074 Wurzburg, Germany
[3] Univ Copenhagen, Dept Drug Design & Pharmacol, Fac Hlth & Med Sci, DK-2100 Copenhagen, Denmark
来源：
CHEMISTRY & BIODIVERSITY | 2014年 / 11卷 / 08期
关键词：
BRUCINE;
D O I：
10.1002/cbdv.201400110
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human 1 and 1 glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC50 value of 1.6M at 1 glycine receptors and 3.7-fold preference towards the 1 subtype. SAR Analysis indicates that the lactam moiety and the C(21)C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors
引用
收藏
页码：1256 / 1262
页数：7
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