Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy
Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy
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DOI：
10.1021/jm700983a
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发表时间：
2007-11-29
影响因子：
7.3
通讯作者：
Geierstanger, Bernhard H.
中科院分区：
文献类型：
--
作者：
Jansma, Ariane;Zhang, Qiong;Geierstanger, Bernhard H.
以天然丰度获得的2D H-1- N-15 HMBC核磁共振和1D H-1核磁共振监测的DMSO滴定证实了分子内氢键的存在，该氢键被设计成模拟一类激酶抑制剂的嘧啶环。在有机溶剂和水溶液中均检测到氢键上的标量偶联，这为检测分子内氢键稳定药物支架中假环的倾向提供了一种简单而通用的方法。
2D H-1- N-15 HMBC NMR acquired at natural abundance and DMSO titration monitored by 1D H-1 NMR verified the existence of an intramolecular hydrogen bond that was designed to mimic the pyrimidinone ring of a class of kinase inhibitors. A scalar coupling across the hydrogen bond was detected in organic and aqueous solvent, suggesting a simple and general approach for testing the propensity of intramolecular hydrogen bonds to stabilize pseudo-rings in drug scaffolds.