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

页码：1256 / 1262

页数：7