Ma Xiang, Poon Thong-Yuen, Wong Peter Tsun Hon, Chui Wai-Keung
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Bioorg Med Chem Lett. 2009 Oct 1;19(19):5644-7. doi: 10.1016/j.bmcl.2009.08.052. Epub 2009 Aug 15.
Neuronal sodium channels blockers interfere with ion flux and have been used for managing neuropathic pain, epilepsy, and cerebral ischemic disorders. In the current study, four groups of 2,4-diamino-1,3,5-triazine derivatives were synthesized and investigated for their neuronal sodium channels binding activity. 5-Aryl-1,3,5-triazaspiro[5.5]undeca-1,3-diene-2,4-diamines (4a-4j) were found to have the best neuronal sodium binding activity among the four groups of triazines evaluated. Derivatives 4a-4j blocked the sodium channels with IC50 values ranged from 4.0 to 14.7 microM. The result from this study showed that analogues of 2,4-diamino-1,3,5-triazines could be used as leads for the discovery of neuronal sodium channels blockers for managing central nervous system related disorders.
神经元钠通道阻滞剂会干扰离子通量，已被用于治疗神经性疼痛、癫痫和脑缺血性疾病。在本研究中，合成了四组2,4-二氨基-1,3,5-三嗪衍生物，并对其神经元钠通道结合活性进行了研究。在评估的四组三嗪中，发现5-芳基-1,3,5-三氮杂螺[5.5]十一碳-1,3-二烯-2,4-二胺（4a-4j）具有最佳的神经元钠结合活性。衍生物4a-4j阻断钠通道的IC50值范围为4.0至14.7微摩尔。本研究结果表明，2,4-二氨基-1,3,5-三嗪类似物可作为发现用于治疗中枢神经系统相关疾病的神经元钠通道阻滞剂的先导化合物。
